Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The unique immunological and microbial aspects of pregnancy

Key Points

  • The immunology of pregnancy has been considered as a host–graft response characterized by immune suppression and consequently a period of increased risk of bacterial and viral infection.

  • However, accumulating evidence suggests that pregnancy is a more complex immunological condition, and thus a reassessment of many the immunological processes evaluated during pregnancy is required.

  • Whereas a successful organ transplant requires constant immunosuppression, a successful pregnancy requires a robust, dynamic and responsive immune system.

  • Embryo implantation and trophoblast invasion require a local inflammatory environment that promotes cell clearance, angiogenesis, cell growth and tolerance.

  • Pregnancy complications, such as preterm birth, are often polymicrobial in nature and can involve viral infections that sensitize the pregnant mother to subsequent bacterial infections.

  • Interferon-β is a crucial immune modulator during pregnancy; it protects the fetus against viral infections and contributes to the process of immune regulation at the maternal–fetal interface.

  • The immune response associated with placental viral infections can affect maternal and fetal survival.

  • Maternal inflammation due to viral or bacterial infections has detrimental consequences for fetal development.

Abstract

The comparison of the immunological state of pregnancy to an immunosuppressed host–graft model continues to lead research and clinical practice to ill-defined approaches. This Review discusses recent evidence that supports the idea that immunological responses at the receptive maternal–fetal interface are not simply suppressed but are instead highly dynamic. We discuss the crucial role of trophoblast cells in shaping not only the way in which immune cells respond to the invading blastocyst but also how they collectively react to external stimuli. We also discuss the role of the microbiota in promoting a tolerogenic maternal immune system and highlight how subclinical viral infections can disrupt this status quo, leading to pregnancy complications.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Immune cells at the maternal–fetal interface.
Figure 2: A comparison of antigen presentation in transplants, tumours and early pregnancy.
Figure 3: Similarities between micrometastasis and blastocyst implantation.
Figure 4: The three immunological stages of pregnancy.
Figure 5: The role of dendritic cells in blastocyst implantation.
Figure 6: Trophoblast-mediated immune regulation.

Similar content being viewed by others

References

  1. Bulmer, J. N., Pace, D. & Ritson, A. Immunoregulatory cells in human decidua: morphology, immunohistochemistry and function. Reprod. Nutr. Dev. 28, 1599–1613 (1988).

    Article  CAS  PubMed  Google Scholar 

  2. Abelius, M. S. et al. The placental immune milieu is characterized by a Th2- and anti-inflammatory transcription profile, regardless of maternal allergy, and associates with neonatal immunity. Am. J. Reprod. Immunol. 73, 445–459 (2015).

    Article  CAS  PubMed  Google Scholar 

  3. Gardner, M. & Luciw, P. Macaque models of human infectious disease. ILAR J. 49, 220–255 (2008).

    Article  CAS  PubMed  Google Scholar 

  4. Fettke, F., Schumacher, A., Costa, S. D. & Zenclussen, A. C. B cells: the old new players in reproductive immunology. Front. Immunol. 5, 285 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Muzzio, D. O. et al. B cell development undergoes profound modifications and adaptations during pregnancy in mice. Biol. Reprod. 91, 115 (2014). This study describes the presence of B cells at the maternal–fetal interface. Prior to the publication of this paper, B cells were thought to be absent from the uterus.

    Article  CAS  PubMed  Google Scholar 

  6. Lessin, D. L., Hunt, J. S., King, C. R. & Wood, G. W. Antigen expression by cells near the maternal–fetal interface. Am. J. Reprod. Immunol. Microbiol. 16, 1–7 (1988).

    Article  CAS  PubMed  Google Scholar 

  7. Medawar, P. Some immunological and endocrinological problems raised by the evolution of viviparity in vertebrates. Symp. Soc. Exp. Biol. 7, 320–338 (1952). This is the seminal paper in which Sir Peter Medawar describes the fetus as a semi-allograft.

    Google Scholar 

  8. Moffett-King, A. Natural killer cells and pregnancy. Nat. Rev. Immunol. 2, 656–663 (2002).

    Article  CAS  PubMed  Google Scholar 

  9. Laskarin, G. et al. Antigen-presenting cells and materno–fetal tolerance: an emerging role for dendritic cells. Am. J. Reprod. Immunol. 58, 255–267 (2007).

    Article  CAS  PubMed  Google Scholar 

  10. Abrahams, V. M., Straszewski-Chavez, S. L., Guller, S. & Mor, G. First trimester trophoblast cells secrete Fas ligand which induces immune cell apoptosis. Mol. Hum. Reprod. 10, 55–63 (2004).

    Article  CAS  PubMed  Google Scholar 

  11. Balkundi, D. R., Hanna, N., Hileb, M., Dougherty, J. & Sharma, S. Labor-associated changes in Fas ligand expression and function in human placenta. Pediatr. Res. 47, 301–308 (2000).

    Article  CAS  PubMed  Google Scholar 

  12. Hanna, J. et al. Decidual NK cells regulate key developmental processes at the human fetal–maternal interface. Nat. Med. 12, 1065–1074 (2006).

    Article  CAS  PubMed  Google Scholar 

  13. Birnberg, T. et al. Dendritic cells are crucial for decidual development during embryo implantation. Am. J. Reprod. Immunol. 57, 342 (2007).

    Google Scholar 

  14. Collins, M. K., Tay, C. S. & Erlebacher, A. Dendritic cell entrapment within the pregnant uterus inhibits immune surveillance of the maternal/fetal interface in mice. J. Clin. Invest. 119, 2062–2073 (2009). This study shows that T cell responses against the fetus and placenta are driven by passive antigen transport, and thus that a tolerogenic mode of antigen presentation predominates when there is negligible input from tissue-resident DCs.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Holtan, S. G., Creedon, D. J., Haluska, P. & Markovic, S. N. Cancer and pregnancy: parallels in growth, invasion, and immune modulation and implications for cancer therapeutic agents. Mayo Clin. Proc. 84, 985–1000 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Beaman, K. D. et al. Pregnancy is a model for tumors, not transplantation. Am. J. Reprod. Immunol. 76, 3–7 (2016).

    Article  PubMed  Google Scholar 

  17. Lin, W. W. & Karin, M. A cytokine-mediated link between innate immunity, inflammation, and cancer. J. Clin. Invest. 117, 1175–1183 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chen, R., Alvero, A. B., Silasi, D. A. & Mor, G. Inflammation, cancer and chemoresistance: taking advantage of the Toll-like receptor signaling pathway. Am. J. Reprod. Immunol. 57, 93–107 (2007).

    Article  CAS  PubMed  Google Scholar 

  19. Allavena, P. et al. Anti-inflammatory properties of the novel antitumor agent Yondelis (Trabectedin): inhibition of macrophage differentiation and cytokine production. Cancer Res. 65, 2964–2971 (2005).

    Article  CAS  PubMed  Google Scholar 

  20. Romero, R. et al. The role of inflammation and infection in preterm birth. Semin. Reprod. Med. 25, 21–39 (2007). This paper provides a detailed description of the role of inflammation during pregnancy and in the initiation of parturition in the context of preterm birth.

    Article  CAS  PubMed  Google Scholar 

  21. Wegmann, T. G. & Guilbert, L. J. Immune signaling at the maternal–fetal interface and trophoblast differentiation. Dev. Comp. Immunol. 16, 425–430 (1992).

    Article  CAS  PubMed  Google Scholar 

  22. Saito, S., Miyazaki, S. & Sasaki, Y. in Immunology of Pregnancy (ed. Mor, G.) 37–48 (Springer New York, 2006).

    Book  Google Scholar 

  23. Chaouat, G. et al. Immune suppression and Th1/Th2 balance in pregnancy revisited: a (very) personal tribute to Tom Wegmann. Am. J. Reprod. Immunol. 37, 427–434 (1997).

    Article  CAS  PubMed  Google Scholar 

  24. Ng, S. C. et al. Expression of intracellular Th1 and Th2 cytokines in women with recurrent spontaneous abortion, implantation failures after IVF/ET or normal pregnancy. Am. J. Reprod. Immunol. 48, 77–86 (2002).

    Article  PubMed  Google Scholar 

  25. Mor, G. & Cardenas, I. The immune system in pregnancy: a unique complexity. Am. J. Reprod. Immunol. 63, 425–433 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Mor, G., Cardenas, I., Abrahams, V. & Guller, S. Inflammation and pregnancy: the role of the immune system at the implantation site. Ann. NY Acad. Sci. 1221, 80–87 (2011).

    Article  CAS  PubMed  Google Scholar 

  27. Norwitz, E. R. et al. Molecular regulation of parturition: the role of the decidual clock. Cold Spring Harb. Perspect. Med. 5, a023143 (2015). This paper discusses the role of the decidua in the initiation of parturition and labour, and introduces the concept of a decidual clock.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Gnainsky, Y. et al. Biopsy-induced inflammatory conditions improve endometrial receptivity: the mechanism of action. Reproduction 149, 75–85 (2015).

    Article  CAS  PubMed  Google Scholar 

  29. Zenclussen, A. C. & Hammerling, G. J. Cellular regulation of the uterine microenvironment that enables embryo implantation. Front. Immunol. 6, 321 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Plaks, V. et al. Uterine DCs are crucial for decidua formation during embryo implantation in mice. J. Clin. Invest. 118, 3954–3965 (2008). This is the first study to show the role of DCs in implantation and decidua formation.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Morelli, A. E. & Thomson, A. W. Tolerogenic dendritic cells and the quest for transplant tolerance. Nat. Rev. Immunol. 7, 610–621 (2007).

    Article  CAS  PubMed  Google Scholar 

  32. Saito, S., Nakashima, A., Shima, T. & Ito, M. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am. J. Reprod. Immunol. 63, 601–610 (2010).

    Article  CAS  PubMed  Google Scholar 

  33. Elovitz, M. A. & Mrinalini, C. Animal models of preterm birth. Trends Endocrinol. Metab. 15, 479–487 (2004).

    Article  CAS  PubMed  Google Scholar 

  34. Faas, M. M. & de Vos, P. Uterine NK cells and macrophages in pregnancy. Placenta http://dx.doi.org/10.1016/j.placenta.2017.03.001 (2017).

  35. Mills, C. D., Kincaid, K., Alt, J. M., Heilman, M. J. & Hill, A. M. M-1/M-2 macrophages and the Th1/Th2 paradigm. J. Immunol. 164, 6166–6173 (2000).

    Article  CAS  PubMed  Google Scholar 

  36. Abrahams, V. M., Kim, Y. M., Straszewski, S. L., Romero, R. & Mor, G. Macrophages and apoptotic cell clearance during pregnancy. Am. J. Reprod. Immunol. 51, 275–282 (2004).

    Article  PubMed  Google Scholar 

  37. Burke, S. D. et al. Uterine NK cells, spiral artery modification and the regulation of blood pressure during mouse pregnancy. Am. J. Reprod. Immunol. 63, 472–481 (2010).

    Article  CAS  PubMed  Google Scholar 

  38. Vacca, P. et al. Crosstalk between decidual NK and CD14+ myelomonocytic cells results in induction of Tregs and immunosuppression. Proc. Natl Acad. Sci. USA 107, 11918–11923 (2010).

    Article  PubMed  Google Scholar 

  39. Tilburgs, T. et al. Human HLA-G+ extravillous trophoblasts: immune-activating cells that interact with decidual leukocytes. Proc. Natl Acad. Sci. USA 112, 7219–7224 (2015).

    Article  CAS  PubMed  Google Scholar 

  40. Erlebacher, A. Mechanisms of T cell tolerance towards the allogeneic fetus. Nat. Rev. Immunol. 13, 23–33 (2013).

    Article  CAS  PubMed  Google Scholar 

  41. Rowe, J. H., Ertelt, J. M., Xin, L. & Way, S. S. Pregnancy imprints regulatory memory that sustains anergy to fetal antigen. Nature 490, 102–106 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Burt, T. D. Fetal regulatory T cells and peripheral immune tolerance in utero: implications for development and disease. Am. J. Reprod. Immunol. 69, 346–358 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Jasper, M. J., Tremellen, K. P. & Robertson, S. A. Primary unexplained infertility is associated with reduced expression of the T-regulatory cell transcription factor Foxp3 in endometrial tissue. Mol. Hum. Reprod. 12, 301–308 (2006). This paper finds reduced expression of FOXP3 in endometrial tissue from women with primary unexplained infertility, which suggests that the impaired differentiation of uterine T cells into T reg cells is a key determinant of fertility in women.

    Article  CAS  PubMed  Google Scholar 

  44. Zenclussen, A. C. et al. Abnormal T-cell reactivity against paternal antigens in spontaneous abortion: adoptive transfer of pregnancy-induced CD4+CD25+ T regulatory cells prevents fetal rejection in a murine abortion model. Am. J. Pathol. 166, 811–822 (2005). This study characterizes the function of T reg cells during pregnancy and their role in the induction of tolerance to paternal antigens.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Sasaki, Y. et al. Decidual and peripheral blood CD4+CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases. Mol. Hum. Reprod. 10, 347–353 (2004).

    Article  CAS  PubMed  Google Scholar 

  46. Lindstrom, T. M. & Bennett, P. R. The role of nuclear factor kappa B in human labour. Reproduction 130, 569–581 (2005).

    Article  CAS  PubMed  Google Scholar 

  47. Edey, L. F. et al. The local and systemic immune response to intrauterine LPS in the prepartum mouse. Biol. Reprod. 95, 125 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Condon, J. C., Jeyasuria, P., Faust, J. M. & Mendelson, C. R. Surfactant protein secreted by the maturing mouse fetal lung acts as a hormone that signals the initiation of parturition. Proc. Natl Acad. Sci. USA 101, 4978–4983 (2004).

    Article  CAS  PubMed  Google Scholar 

  49. Plazyo, O. et al. HMGB1 induces an inflammatory response in the chorioamniotic membranes that is partially mediated by the inflammasome. Biol. Reprod. 95, 130 (2016). The results of this study provide insights into the mechanisms by which HMGB1 induces preterm labour and birth in mice, and explain why the concentration of alarmins is increased in women who undergo spontaneous preterm labour.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Behnia, F., Sheller, S. & Menon, R. Mechanistic differences leading to infectious and sterile inflammation. Am. J. Reprod. Immunol. 75, 505–518 (2016).

    Article  CAS  PubMed  Google Scholar 

  51. Jeyasuria, P., Subedi, K., Suresh, A. & Condon, J. C. Elevated levels of uterine anti-apoptotic signaling may activate NFKB and potentially confer resistance to caspase 3-mediated apoptotic cell death during pregnancy in mice. Biol. Reprod. 85, 417–424 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Gomez-Lopez, N. et al. Intra-amniotic administration of HMGB1 induces spontaneous preterm labor and birth. Am. J. Reprod. Immunol. 75, 3–7 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Obata, Y., Furusawa, Y. & Hase, K. Epigenetic modifications of the immune system in health and disease. Immunol. Cell Biol. 93, 226–232 (2015).

    Article  CAS  PubMed  Google Scholar 

  54. Bidarimath, M., Khalaj, K., Wessels, J. M. & Tayade, C. MicroRNAs, immune cells and pregnancy. Cell. Mol. Immunol. 11, 538–547 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Parham, P. & Moffett, A. Variable NK cell receptors and their MHC class I ligands in immunity, reproduction and human evolution. Nat. Rev. Immunol. 13, 133–144 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ramhorst, R. et al. Modulation and recruitment of inducible regulatory T cells by first trimester trophoblast cells. Am. J. Reprod. Immunol. 67, 17–27 (2012).

    Article  CAS  PubMed  Google Scholar 

  57. Romero, R. et al. The preterm parturition syndrome. BJOG 113 (Suppl. 3), 17–42 (2006).

    Article  CAS  PubMed  Google Scholar 

  58. Manaster, I. et al. Endometrial NK cells are special immature cells that await pregnancy. J. Immunol. 181, 1869–1876 (2008).

    Article  CAS  PubMed  Google Scholar 

  59. Zhang, J., Chen, Z., Smith, G. N. & Croy, B. A. Natural killer cell-triggered vascular transformation: maternal care before birth? Cell. Mol. Immunol. 8, 1–11 (2011).

    Article  CAS  PubMed  Google Scholar 

  60. Aldo, P. B. et al. Trophoblast induces monocyte differentiation into CD14+/CD16+ macrophages. Am. J. Reprod. Immunol. 72, 270–284 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Svensson-Arvelund, J. et al. The human fetal placenta promotes tolerance against the semiallogeneic fetus by inducing regulatory T cells and homeostatic M2 macrophages. J. Immunol. 194, 1534–1544 (2015).

    Article  CAS  PubMed  Google Scholar 

  62. Repnik, U. et al. Comparison of macrophage phenotype between decidua basalis and decidua parietalis by flow cytometry. Placenta 29, 405–412 (2008).

    Article  CAS  PubMed  Google Scholar 

  63. Houser, B. L., Tilburgs, T., Hill, J., Nicotra, M. L. & Strominger, J. L. Two unique human decidual macrophage populations. J. Immunol. 186, 2633–2642 (2011). This study characterizes the phenotype of decidual macrophages.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Oettel, A. et al. Human umbilical vein endothelial cells foster conversion of CD4+CD25Foxp3 T cells into CD4+Foxp3+ regulatory T cells via transforming growth factor-β. Sci. Rep. 6, 23278 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Poloski, E. et al. JEG-3 trophoblast cells producing human chorionic gonadotropin promote conversion of human CD4+FOXP3 T cells into CD4+FOXP3+ regulatory T cells and foster T cell suppressive activity. Biol. Reprod. 94, 106 (2016).

    Article  CAS  PubMed  Google Scholar 

  66. Nancy, P. et al. Chemokine gene silencing in decidual stromal cells limits T cell access to the maternal–fetal interface. Science 336, 1317–1321 (2012). This study demonstrates the role of the decidua in the recruitment of immune cells and the regulation of this process by epigenetic factors.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Lockwood, C. J. et al. Decidual cell regulation of natural killer cell-recruiting chemokines: implications for the pathogenesis and prediction of preeclampsia. Am. J. Pathol. 183, 841–856 (2013). This report demonstrates the ability of stromal cells to recognize and respond to microorganisms, and the potential role of these processes in pregnancy complications.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Janeway, C. A. Jr & Medzhitov, R. Innate immune recognition. Annu. Rev. Immunol. 20, 197–216 (2002).

    Article  CAS  PubMed  Google Scholar 

  69. Medzhitov, R. & Janeway, C. Jr. Innate immunity. N. Engl. J. Med. 343, 338–344 (2000).

    Article  CAS  PubMed  Google Scholar 

  70. Abrahams, V. M. et al. A role for TLRs in the regulation of immune cell migration by first trimester trophoblast cells. J. Immunol. 175, 8096–8104 (2005).

    Article  CAS  PubMed  Google Scholar 

  71. Abrahams, V. M., Romero, R. & Mor, G. TLR-3 and TLR-4 mediate differential chemokine production and immune cell recruitment by first trimester trophoblast cells. Am. J. Reprod. Immunol. 53, 279 (2005).

    Article  Google Scholar 

  72. Abrahams, V. M. et al. Stimulation of first trimester trophoblast cells with poly(I:C) induces SLPI secretion. Am. J. Reprod. Immunol. 53, 280 (2005).

    Google Scholar 

  73. Mor, G., Romero, R., Aldo, P. B. & Abrahams, V. M. Is the trophoblast an immune regulator?: the role of Toll-like receptors during pregnancy. Crit. Rev. Immunol. 25, 375–388 (2005).

    Article  CAS  PubMed  Google Scholar 

  74. Costello, M. J., Joyce, S. K. & Abrahams, V. M. NOD protein expression and function in first trimester trophoblast cells. Am. J. Reprod. Immunol. 57, 67–80 (2007).

    Article  CAS  PubMed  Google Scholar 

  75. Romero, R., Chaiworapongsa, T. & Espinoza, J. Micronutrients and intrauterine infection, preterm birth and the fetal inflammatory response syndrome. J. Nutr. 133, 1668S–1673S (2003).

    Article  CAS  PubMed  Google Scholar 

  76. Espinoza, J., Erez, O. & Romero, R. Preconceptional antibiotic treatment to prevent preterm birth in women with a previous preterm delivery. Am. J. Obstet. Gynecol. 194, 630–637 (2006).

    Article  CAS  PubMed  Google Scholar 

  77. Goldenberg, R. L., Hauth, J. C. & Andrews, W. W. Intrauterine infection and preterm delivery. N. Engl. J. Med. 342, 1500–1507 (2000).

    Article  CAS  PubMed  Google Scholar 

  78. Lamont, R. F. The role of infection in preterm labour and birth. Hosp. Med. 64, 644–647 (2003).

    Article  PubMed  Google Scholar 

  79. Kiefer, D. G. et al. Is midtrimester short cervix a sign of intraamniotic inflammation? Am. J. Obstet. Gynecol. 200, 374.e1–374.e5 (2009).

    Article  Google Scholar 

  80. Peltier, M. R. et al. Polybrominated diphenyl ethers enhance the production of proinflammatory cytokines by the placenta. Placenta 33, 745–749 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Wang, H. & Hirsch, E. Bacterially-induced preterm labor and regulation of prostaglandin-metabolizing enzyme expression in mice: the role of Toll-like receptor 4. Biol. Reprod. 69, 1957–1963 (2003).

    Article  CAS  PubMed  Google Scholar 

  82. Agrawal, V., Smart, K., Jilling, T. & Hirsch, E. Surfactant protein (SP)-A suppresses preterm delivery and inflammation via TLR2. PLoS ONE 8, e63990 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Bayraktar, M. et al. IL-10 modulates placental responses to TLR ligands. Am. J. Reprod. Immunol. 62, 390–399 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kiefer, D. G. et al. Amniotic fluid inflammatory score is associated with pregnancy outcome in patients with mid trimester short cervix. Am. J. Obstet. Gynecol. 206, 68.e1–68.e6 (2012).

    Article  Google Scholar 

  85. Straszewski-Chavez, S. L., Abrahams, V. M. & Mor, G. The role of apoptosis in the regulation of trophoblast survival and differentiation during pregnancy. Endocr. Rev. 26, 877–897 (2005).

    Article  CAS  PubMed  Google Scholar 

  86. Mor, G. Pregnancy reconceived. Nat. Hist. 116, 36–41 (2007).

    Google Scholar 

  87. Abrahams, V. M. & Mor, G. Toll-like receptors and their role in the trophoblast. Placenta 26, 540–547 (2005).

    Article  CAS  PubMed  Google Scholar 

  88. Adams Waldorf, K. M., Rubens, C. E. & Gravett, M. G. Use of nonhuman primate models to investigate mechanisms of infection-associated preterm birth. BJOG 118, 136–144 (2011).

    Article  CAS  PubMed  Google Scholar 

  89. Koga, K. & Mor, G. Toll-like receptors at the maternal–fetal interface in normal pregnancy and pregnancy disorders. Am. J. Reprod. Immunol. 63, 587–600 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Elovitz, M. A., Mrinalini, C. & Sammel, M. D. Elucidating the early signal transduction pathways leading to fetal brain injury in preterm birth. Pediatr. Res. 59, 50–55 (2006).

    Article  PubMed  Google Scholar 

  91. Burd, I. et al. Inflammation-induced preterm birth alters neuronal morphology in the mouse fetal brain. J. Neurosci. Res. 88, 1872–1881 (2010). This study suggests that inflammation-induced preterm birth, and not the process of preterm birth itself, may result in neuroinflammation and alter fetal neuronal morphology.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Pirianov, G. et al. The cyclopentenone 15-deoxy-δ 12,14-prostaglandin J2 delays lipopolysaccharide-induced preterm delivery and reduces mortality in the newborn mouse. Endocrinology 150, 699–706 (2009).

    Article  CAS  PubMed  Google Scholar 

  93. Koga, K. et al. Activation of TLR3 in the trophoblast is associated with preterm delivery. Am. J. Reprod. Immunol. 61, 196–212 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Cardenas, I. et al. Nod1 activation by bacterial iE-DAP induces maternal–fetal inflammation and preterm labor. J. Immunol. 187, 980–986 (2011).

    Article  CAS  PubMed  Google Scholar 

  95. Pettker, C. M. et al. Value of placental microbial evaluation in diagnosing intra-amniotic infection. Obstet. Gynecol. 109, 739–749 (2007).

    Article  PubMed  Google Scholar 

  96. Goldenberg, R. L., Culhane, J. F., Iams, J. D. & Romero, R. Epidemiology and causes of preterm birth. Lancet 371, 75–84 (2008).

    Article  PubMed  Google Scholar 

  97. Digiulio, D. B. et al. Microbial invasion of the amniotic cavity in preeclampsia as assessed by cultivation and sequence-based methods. J. Perinat. Med. 38, 503–513 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Cao, B. & Mysorekar, I. U. Intracellular bacteria in placental basal plate localize to extravillous trophoblasts. Placenta 35, 139–142 (2014).

    Article  CAS  PubMed  Google Scholar 

  99. Stout, M. J. et al. Identification of intracellular bacteria in the basal plate of the human placenta in term and preterm gestations. Am. J. Obstet. Gynecol. 208, 226.e1–226.e7 (2013).

    Article  Google Scholar 

  100. Racicot, K. et al. Viral infection of the pregnant cervix predisposes to ascending bacterial infection. J. Immunol. 191, 934–941 (2013). This study demonstrates that a viral infection of the cervix has consequences for protection against ascending bacteria during pregnancy.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Aagaard, K. et al. The placenta harbors a unique microbiome. Sci. Transl Med. 6, 237ra65 (2014). This study characterizes the normal microbiome during pregnancy.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Prince, A. L., Antony, K. M., Chu, D. M. & Aagaard, K. M. The microbiome, parturition, and timing of birth: more questions than answers. J. Reprod. Immunol. 104–105, 12–19 (2014).

  103. Prince, A. L., Antony, K. M., Ma, J. & Aagaard, K. M. The microbiome and development: a mother's perspective. Semin. Reprod. Med. 32, 14–22 (2014).

    Article  PubMed  Google Scholar 

  104. Ramos Bde, A., Kanninen, T. T., Sisti, G. & Witkin, S. S. Microorganisms in the female genital tract during pregnancy: tolerance versus pathogenesis. Am. J. Reprod. Immunol. 73, 383–389 (2015).

    Article  PubMed  Google Scholar 

  105. Wen, L. et al. Innate immunity and intestinal microbiota in the development of type 1 diabetes. Nature 455, 1109–1113 (2008). The study shows that the interaction of the intestinal microbes with the innate immune system is a crucial epigenetic factor that modifies an individual's predisposition to type 1 diabetes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Hu, Y. et al. Different immunological responses to early-life antibiotic exposure affecting autoimmune diabetes development in NOD mice. J. Autoimmun. 72, 47–56 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Gomez de Aguero, M. et al. The maternal microbiota drives early postnatal innate immune development. Science 351, 1296–1302 (2016). This study investigates the role of the maternal microbiota, and shows that pups born to mothers transiently colonized in pregnancy are better able to avoid inflammatory responses to microbial molecules and the penetration of intestinal microbes than are pups born to mothers that had not been transiently colonized.

    Article  CAS  PubMed  Google Scholar 

  108. Ivashkiv, L. B. & Donlin, L. T. Regulation of type I interferon responses. Nat. Rev. Immunol. 14, 36–49 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Chard, T., Craig, P. H., Menabawey, M. & Lee, C. Alpha interferon in human pregnancy. Br. J. Obstet. Gynaecol. 93, 1145–1149 (1986).

    Article  CAS  PubMed  Google Scholar 

  110. Howatson, A. G., Farquharson, M., Meager, A., McNicol, A. M. & Foulis, A. K. Localization of α-interferon in the human feto–placental unit. J. Endocrinol. 119, 531–534 (1988).

    Article  CAS  PubMed  Google Scholar 

  111. Aboagye-Mathiesen, G., Toth, F. D., Zdravkovic, M. & Ebbesen, P. Functional characteristics of human trophoblast interferons. Am. J. Reprod. Immunol. 35, 309–317 (1996).

    Article  CAS  PubMed  Google Scholar 

  112. Aboagye-Mathiesen, G., Toth, F. D., Zdravkovic, M. & Ebbesen, P. Human trophoblast interferons: production and possible roles in early pregnancy. Early Pregnancy 1, 41–53 (1995).

    CAS  PubMed  Google Scholar 

  113. Lee, B. N. et al. Production of interferons and β-chemokines by placental trophoblasts of HIV-1-infected women. Infect. Dis. Obstet. Gynecol. 9, 95–104 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Reuben, J. M. et al. Induction of inflammatory cytokines in placental monocytes of gravidae infected with the human immunodeficiency virus type 1. J. Interferon Cytokine Res. 16, 963–971 (1996).

    Article  CAS  PubMed  Google Scholar 

  115. Odorizzi, P. M. & Wherry, E. J. Immunology. An interferon paradox. Science 340, 155–156 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Sharif, M. N. et al. Twist mediates suppression of inflammation by type I IFNs and Axl. J. Exp. Med. 203, 1891–1901 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Racicot, K. et al. Type I interferon regulates the placental inflammatory response to bacteria and is targeted by virus: mechanism of polymicrobial infection-induced preterm birth. Am. J. Reprod. Immunol. 75, 451–460 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Boasso, A., Hardy, A. W., Anderson, S. A., Dolan, M. J. & Shearer, G. M. HIV-induced type I interferon and tryptophan catabolism drive T cell dysfunction despite phenotypic activation. PLoS ONE 3, e2961 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Wilson, E. B. & Brooks, D. G. Decoding the complexity of type I interferon to treat persistent viral infections. Trends Microbiol. 21, 634–640 (2013).

    Article  CAS  PubMed  Google Scholar 

  120. Wilson, E. B. et al. Blockade of chronic type I interferon signaling to control persistent LCMV infection. Science 340, 202–207 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Iwasaki, A. Antiviral immune responses in the genital tract: clues for vaccines. Nat. Rev. Immunol. 10, 699–711 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Iwasaki, A. & Medzhitov, R. Regulation of adaptive immunity by the innate immune system. Science 327, 291–295 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Tian, M. et al. The PD-1/PD-L1 inhibitory pathway is altered in pre-eclampsia and regulates T cell responses in pre-eclamptic rats. Sci. Rep. 6, 27683 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Silasi, M. et al. Viral infections during pregnancy. Am. J. Reprod. Immunol. 73, 199–213 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  125. Giugliano, S. et al. Hepatitis C virus sensing by human trophoblasts induces innate immune responses and recruitment of maternal NK cells: potential implications for limiting vertical transmission. J. Immunol. 195, 3737–3747 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Coyne, C. B. & Lazear, H. M. Zika virus — reigniting the TORCH. Nat. Rev. Microbiol. 14, 707–715 (2016).

    Article  CAS  PubMed  Google Scholar 

  127. Olivadoti, M., Toth, L. A., Weinberg, J. & Opp, M. R. Murine gammaherpesvirus 68: a model for the study of Epstein–Barr virus infections and related diseases. Comp. Med. 57, 44–50 (2007).

    CAS  PubMed  Google Scholar 

  128. Dutia, B. M., Allen, D. J., Dyson, H. & Nash, A. A. Type I interferons and IRF-1 play a critical role in the control of a gammaherpesvirus infection. Virology 261, 173–179 (1999).

    Article  CAS  PubMed  Google Scholar 

  129. Garcia-Sastre, A. & Biron, C. A. Type 1 interferons and the virus–host relationship: a lesson in detente. Science 312, 879–882 (2006).

    Article  CAS  PubMed  Google Scholar 

  130. Cardenas, I. et al. Viral infection of the placenta leads to fetal inflammation and sensitization to bacterial products predisposing to preterm labor. J. Immunol. 185, 1248–1257 (2010). This study demonstrates that viral infection of the placenta may sensitize the pregnant mother to bacterial products and promote preterm labour.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Cappelletti, M. et al. Inflammation and preterm birth. J. Leukoc. Biol. 99, 67–78 (2016).

    Article  CAS  PubMed  Google Scholar 

  132. Romero, R. et al. CXCL10 and IL-6: markers of two different forms of intra-amniotic inflammation in preterm labor. Am. J. Reprod. Immunol. http://dx.doi.org/10.1111/aji.12685 (2017).

  133. Cardenas, I. et al. Placental viral infection sensitizes to endotoxin-induced pre-term labor: a double hit hypothesis. Am. J. Reprod. Immunol. 65, 110–117 (2011). This study proposes the double-hit hypothesis to explain the inflammatory response associated with preterm labour.

    Article  CAS  PubMed  Google Scholar 

  134. Cappelletti, M. et al. Type I interferons regulate susceptibility to inflammation-induced preterm birth. JCI Insight 2, e91288 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  135. Gervasi, M. T. et al. Viral invasion of the amniotic cavity (VIAC) in the midtrimester of pregnancy. J. Matern. Fetal Neonatal Med. 25, 2002–2013 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Kourtis, A. P., Read, J. S. & Jamieson, D. J. Pregnancy and infection. N. Engl. J. Med. 370, 2211–2218 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Kwon, J. Y., Romero, R. & Mor, G. New insights into the relationship between viral infection and pregnancy complications. Am. J. Reprod. Immunol. 71, 387–390 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  138. Price, M. E., Fisher-Hoch, S. P., Craven, R. B. & McCormick, J. B. A prospective study of maternal and fetal outcome in acute Lassa fever infection during pregnancy. BMJ 297, 584–587 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Jamieson, D. J., Uyeki, T. M., Callaghan, W. M., Meaney-Delman, D. & Rasmussen, S. A. What obstetrician-gynecologists should know about Ebola: a perspective from the Centers for Disease Control and Prevention. Obstet. Gynecol. 124, 1005–1010 (2014).

    Article  PubMed  Google Scholar 

  140. Berry, S. M. et al. Premature parturition is characterized by in utero activation of the fetal immune system. Am. J. Obstet. Gynecol. 173, 1315–1320 (1995).

    Article  CAS  PubMed  Google Scholar 

  141. Faucher, B. et al. Long-term ocular outcome in congenital toxoplasmosis: a prospective cohort of treated children. J. Infect. 64, 104–109 (2012).

    Article  CAS  PubMed  Google Scholar 

  142. Knuesel, I. et al. Maternal immune activation and abnormal brain development across CNS disorders. Nat. Rev. Neurol. 10, 643–660 (2014).

    Article  CAS  PubMed  Google Scholar 

  143. Cordeiro, C. N., Tsimis, M. & Burd, I. Infections and brain development. Obstet. Gynecol. Surv. 70, 644–655 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  144. Estes, M. L. & McAllister, A. K. Maternal immune activation: implications for neuropsychiatric disorders. Science 353, 772–777 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Rose, D. R. et al. Long-term altered immune responses following fetal priming in a non-human primate model of maternal immune activation. Brain Behav. Immun. 63, 60–70 (2017).

    Article  CAS  PubMed  Google Scholar 

  146. Zuckerman, L., Rehavi, M., Nachman, R. & Weiner, I. Immune activation during pregnancy in rats leads to a postpubertal emergence of disrupted latent inhibition, dopaminergic hyperfunction, and altered limbic morphology in the offspring: a novel neurodevelopmental model of schizophrenia. Neuropsychopharmacology 28, 1778–1789 (2003).

    Article  CAS  PubMed  Google Scholar 

  147. Smith, S. E., Li, J., Garbett, K., Mirnics, K. & Patterson, P. H. Maternal immune activation alters fetal brain development through interleukin-6. J. Neurosci. 27, 10695–10702 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Garbett, K. A., Hsiao, E. Y., Kalman, S., Patterson, P. H. & Mirnics, K. Effects of maternal immune activation on gene expression patterns in the fetal brain. Transl Psychiatry 2, e98 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Shi, L., Fatemi, S. H., Sidwell, R. W. & Patterson, P. H. Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. J. Neurosci. 23, 297–302 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  150. Shi, L. et al. Activation of the maternal immune system alters cerebellar development in the offspring. Brain Behav. Immun. 23, 116–123 (2009).

    Article  CAS  PubMed  Google Scholar 

  151. Shi, L., Tu, N. & Patterson, P. H. Maternal influenza infection is likely to alter fetal brain development indirectly: the virus is not detected in the fetus. Int. J. Dev. Neurosci. 23, 299–305 (2005).

    Article  PubMed  Google Scholar 

  152. Korzeniewski, S. J. et al. A “multi-hit” model of neonatal white matter injury: cumulative contributions of chronic placental inflammation, acute fetal inflammation and postnatal inflammatory events. J. Perinat. Med. 42, 731–743 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  153. Mahic, M. et al. Maternal immunoreactivity to herpes simplex virus 2 and risk of autism spectrum disorder in male offspring. mSphere 2, e00016–17 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Price, M., Fisher-Hoch, S., Craven, R. & McCormick, J. A prospective study of maternal and fetal outcome in acute Lassa fever infection during pregnancy. BMJ 297, 584–587 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Bello, O. O., Akinajo, O. R., Odubamowo, K. H. & Oluwasola, T. A. Lassa fever in pregnancy: report of 2 cases seen at the University College Hospital, Ibadan. Case Rep. Obstet. Gynecol. 2016, 9673683 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Racicot, K. et al. Cutting edge: fetal/placental type I IFN can affect maternal survival and fetal viral load during viral infection. J. Immunol. 198, 3029–3032 (2017). The findings of this study highlight the role of fetal–placental type I IFNs in the modulation of viral infection in the mother and fetus.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. de Carvalho, N. S., de Carvalho, B. F., Fugaca, C. A., Doris, B. & Biscaia, E. S. Zika virus infection during pregnancy and microcephaly occurrence: a review of literature and Brazilian data. Braz. J. Infect. Dis. 20, 282–289 (2016).

    Article  PubMed  Google Scholar 

  158. Dyer, O. US agency says Zika virus causes microcephaly. BMJ 353, i2167 (2016).

    Article  PubMed  Google Scholar 

  159. Garcez, P. P. et al. Zika virus impairs growth in human neurospheres and brain organoids. Science 352, 816–818 (2016). The results of this study suggest that Zika virus abrogates neurogenesis during human brain development.

    Article  CAS  PubMed  Google Scholar 

  160. Mor, G. Placental inflammatory response to Zika virus may affect fetal brain development. Am. J. Reprod. Immunol. 75, 421–422 (2016).

    Article  PubMed  Google Scholar 

  161. Dekel, N., Gnainsky, Y., Granot, I. & Mor, G. Inflammation and implantation. Am. J. Reprod. Immunol. 63, 17–21 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Syggelou, A., Iacovidou, N., Kloudas, S., Christoni, Z. & Papaevangelou, V. Congenital cytomegalovirus infection. Ann. NY Acad. Sci. 1205, 144–147 (2010).

    Article  PubMed  Google Scholar 

  163. Picone, O. et al. A series of 238 cytomegalovirus primary infections during pregnancy: description and outcome. Prenat. Diagn. 33, 751–758 (2013).

    Article  CAS  PubMed  Google Scholar 

  164. Chernyshov, V., Slukvin, I. & Bondarenko, G. Phenotypic characterization of CD7+, CD3+, and CD8+ lymphocytes from first trimester human decidua using two color flow cytometry. Am. J. Reprod. Immunol. 29, 5–16 (1993).

    Article  CAS  PubMed  Google Scholar 

  165. Enders, G., Miller, E., Cradock-Watson, J., Bolley, I. & Ridehalgh, M. Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases. Lancet 343, 1548–1551 (1994).

    Article  CAS  PubMed  Google Scholar 

  166. Pastuszak, A. L. et al. Outcome after maternal varicella infection in the first 20 weeks of pregnancy. N. Engl. J. Med. 330, 901–905 (1994).

    Article  CAS  PubMed  Google Scholar 

  167. Dontigny, L. et al. Rubella in pregnancy. J. Obstet. Gynaecol. Can. 30, 152–168 (2008).

    Article  PubMed  Google Scholar 

  168. Lee, J. Y. & Bowden, D. S. Rubella virus replication and links to teratogenicity. Clin. Microbiol. Rev. 13, 571–587 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Brown, Z. A. et al. The acquisition of herpes simplex virus during pregnancy. N. Engl. J. Med. 337, 509–515 (1997).

    Article  CAS  PubMed  Google Scholar 

  170. Xu, F., Markowitz, L. E., Gottlieb, S. L. & Berman, S. M. Seroprevalence of herpes simplex virus types 1 and 2 in pregnant women in the United States. Am. J. Obstet. Gynecol. 196, 43.e1–43.e6 (2007).

    Article  Google Scholar 

  171. Ciaranello, A. L. et al. What will it take to eliminate pediatric HIV? Reaching WHO target rates of mother-to-child HIV transmission in Zimbabwe: a model-based analysis. PLoS Med. 9, e1001156 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  172. Wang, B. et al. Loss to follow-up in a community clinic in South Africa — roles of gender, pregnancy and CD4 count. S. Afr. Med. J. 101, 253–257 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  173. Leikin, E., Lysikiewicz, A., Garry, D. & Tejani, N. Intrauterine transmission of hepatitis A virus. Obstet. Gynecol. 88, 690–691 (1996).

    Article  CAS  PubMed  Google Scholar 

  174. Erkan, T., Kutlu, T., Cullu, F. & Tumay, G. T. A case of vertical transmission of hepatitis A virus infection. Acta Paediatr. 87, 1008–1009 (1998).

    Article  CAS  PubMed  Google Scholar 

  175. Guo, Z. et al. Risk factors of HBV intrauterine transmission among HBsAg-positive pregnant women. J. Viral Hepat. 20, 317–321 (2013).

    Article  CAS  PubMed  Google Scholar 

  176. Bai, X. et al. Potential roles of placental human β-defensin-3 and apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3G in prevention of intrauterine transmission of hepatitis B virus. J. Med. Virol. 87, 375–379 (2015).

    Article  CAS  PubMed  Google Scholar 

  177. Yeung, L. T., King, S. M. & Roberts, E. A. Mother-to-infant transmission of hepatitis C virus. Hepatology 34, 223–229 (2001).

    Article  CAS  PubMed  Google Scholar 

  178. Slowik, M. K. & Jhaveri, R. Hepatitis B and C viruses in infants and young children. Semin. Pediatr. Infect. Dis. 16, 296–305 (2005).

    Article  PubMed  Google Scholar 

  179. Patra, S., Kumar, A., Trivedi, S. S., Puri, M. & Sarin, S. K. Maternal and fetal outcomes in pregnant women with acute hepatitis E virus infection. Ann. Intern. Med. 147, 28–33 (2007).

    Article  PubMed  Google Scholar 

  180. Neuzil, K. M., Reed, G. W., Mitchel, E. F., Simonsen, L. & Griffin, M. R. Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. Am. J. Epidemiol. 148, 1094–1102 (1998).

    Article  CAS  PubMed  Google Scholar 

  181. Siston, A. M. et al. Pandemic 2009 influenza A(H1N1) virus illness among pregnant women in the United States. JAMA 303, 1517–1525 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Schuler-Faccini, L. et al. Zika virus: a new human teratogen? Implications for women of reproductive age. Clin. Pharmacol. Ther. 100, 28–30 (2016).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gil Mor.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

FURTHER INFORMATION

Mouse gammaherpesvirus 68

PowerPoint slides

Glossary

Myometrium

The middle layer of the uterine wall. It comprises mainly smooth muscle cells (also known as uterine myocytes) and supporting stromal and vascular tissue, and its main function is to induce uterine contractions during labour.

Chorioamnionitis

Inflammation of the fetal membranes (amnion and chorion) due to a bacterial infection. It typically results from bacteria ascending into the uterus from the vagina and is most often associated with prolonged labour.

Maternal immune activation

A state in which maternal serum cytokine concentrations are elevated. This state is thought to cause neurological deficits in the offspring.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mor, G., Aldo, P. & Alvero, A. The unique immunological and microbial aspects of pregnancy. Nat Rev Immunol 17, 469–482 (2017). https://doi.org/10.1038/nri.2017.64

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nri.2017.64

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing