The Unique Immunological and Microbial Aspects of Pregnancy

Overview

Journal Nat Rev Immunol

Specialty Allergy & Immunology

Date 2017 Jun 20

PMID 28627518

Citations 423

Authors

Gil Mor

Paulomi Aldo

Ayesha B Alvero

Affiliations

Soon will be listed here.

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.

Citing Articles

Congenital Zika virus infection in laboratory animals: a comparative review highlights translational studies on the maternal-foetal interface.

Gardinali N, Marchevsky R, Vieira Y, Pelajo-Machado M, Kugelmeier T, Melgaco J Mem Inst Oswaldo Cruz. 2025; 120:e240125.

PMID: 40052994 PMC: 11884655. DOI: 10.1590/0074-02760240125.

Microbiota Dysbiosis: A Key Modulator in Preeclampsia Pathogenesis and Its Therapeutic Potential.

Torres-Torres J, Basurto-Serrano J, Camacho-Martinez Z, Guadarrama-Sanchez F, Monroy-Munoz I, Perez-Duran J Microorganisms. 2025; 13(2).

PMID: 40005611 PMC: 11857279. DOI: 10.3390/microorganisms13020245.

Reference Intervals for Common Biochemistry and Hematology Parameters in Early Pregnancy-A Prospective Study.

Supak-Smolcic V, Franin L, Antoncic D, Matejcic S, Vrdoljak-Colo I, Homar S Diagnostics (Basel). 2025; 15(4).

PMID: 40002566 PMC: 11854365. DOI: 10.3390/diagnostics15040415.

Hemostatic Profile and Serum Levels of Interferon Gamma-Induced Protein 10 (IP-10) in Neonates Born to Mothers with COVID-19 During the Peripartum Period.

Sokou R, Bikouli E, Tsantes A, Halvatsiotis P, Houhoula D, Taliaka Kopanou P Int J Mol Sci. 2025; 26(3).

PMID: 39940970 PMC: 11818117. DOI: 10.3390/ijms26031201.

Do endometrial immune changes with age prior to menopause compromise fertility in women?.

Patel M, Shen Z, Wira C Explor Immunol. 2025; 2(5):677-692.

PMID: 39931230 PMC: 11809571. DOI: 10.37349/ei.2022.00076.

References

Burke S, Barrette V, Gravel J, Carter A, Hatta K, Zhang J . Uterine NK cells, spiral artery modification and the regulation of blood pressure during mouse pregnancy. Am J Reprod Immunol. 2010; 63(6):472-81. DOI: 10.1111/j.1600-0897.2010.00818.x. View

Romero R, Chaemsaithong P, Chaiyasit N, Docheva N, Dong Z, Kim C . CXCL10 and IL-6: Markers of two different forms of intra-amniotic inflammation in preterm labor. Am J Reprod Immunol. 2017; 78(1). PMC: 5488235. DOI: 10.1111/aji.12685. View

Tilburgs T, Crespo A, van der Zwan A, Rybalov B, Raj T, Stranger B . Human HLA-G+ extravillous trophoblasts: Immune-activating cells that interact with decidual leukocytes. Proc Natl Acad Sci U S A. 2015; 112(23):7219-24. PMC: 4466754. DOI: 10.1073/pnas.1507977112. View

Abelius M, Janefjord C, Ernerudh J, Berg G, Matthiesen L, Duchen K . 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. 2014; 73(5):445-59. DOI: 10.1111/aji.12350. View

Fettke F, Schumacher A, Costa S, Zenclussen A . B cells: the old new players in reproductive immunology. Front Immunol. 2014; 5:285. PMC: 4066365. DOI: 10.3389/fimmu.2014.00285. View

Cordeiro C, Tsimis M, Burd I . Infections and Brain Development. Obstet Gynecol Surv. 2015; 70(10):644-55. PMC: 4795171. DOI: 10.1097/OGX.0000000000000236. View

Garcez P, Loiola E, Madeiro da Costa R, Higa L, Trindade P, Delvecchio R . Zika virus impairs growth in human neurospheres and brain organoids. Science. 2016; 352(6287):816-8. DOI: 10.1126/science.aaf6116. View

DiGiulio D, Gervasi M, Romero R, Mazaki-Tovi S, Vaisbuch E, Kusanovic J . Microbial invasion of the amniotic cavity in preeclampsia as assessed by cultivation and sequence-based methods. J Perinat Med. 2010; 38(5):503-13. PMC: 3325506. DOI: 10.1515/jpm.2010.078. View

Plazyo O, Romero R, Unkel R, Balancio A, Mial T, Xu Y . HMGB1 Induces an Inflammatory Response in the Chorioamniotic Membranes That Is Partially Mediated by the Inflammasome. Biol Reprod. 2016; 95(6):130. PMC: 5315428. DOI: 10.1095/biolreprod.116.144139. View

10.

Leikin E, Lysikiewicz A, Garry D, Tejani N . Intrauterine transmission of hepatitis A virus. Obstet Gynecol. 1996; 88(4 Pt 2):690-1. DOI: 10.1016/0029-7844(96)00259-1. View

11.

Bai X, Tian T, Wang P, Yang X, Wang Z, Dong M . Potential roles of placental human beta-defensin-3 and apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3G in prevention of intrauterine transmission of hepatitis B virus. J Med Virol. 2014; 87(3):375-9. DOI: 10.1002/jmv.24072. View

12.

Repnik U, Tilburgs T, Roelen D, van der Mast B, Kanhai H, Scherjon S . Comparison of macrophage phenotype between decidua basalis and decidua parietalis by flow cytometry. Placenta. 2008; 29(5):405-12. DOI: 10.1016/j.placenta.2008.02.004. View

13.

de Carvalho N, de Carvalho B, Fugaca C, Doris B, Silverio Biscaia E . Zika virus infection during pregnancy and microcephaly occurrence: a review of literature and Brazilian data. Braz J Infect Dis. 2016; 20(3):282-9. PMC: 9425494. DOI: 10.1016/j.bjid.2016.02.006. View

14.

Beaman K, Jaiswal M, Katara G, Kulshreshta A, Pamarthy S, Ibrahim S . Pregnancy is a model for tumors, not transplantation. Am J Reprod Immunol. 2016; 76(1):3-7. DOI: 10.1111/aji.12524. View

15.

Prince A, Antony K, Ma J, Aagaard K . The microbiome and development: a mother's perspective. Semin Reprod Med. 2014; 32(1):14-22. DOI: 10.1055/s-0033-1361818. View

16.

Laskarin G, Kammerer U, Rukavina D, Thomson A, Fernandez N, Blois S . Antigen-presenting cells and materno-fetal tolerance: an emerging role for dendritic cells. Am J Reprod Immunol. 2007; 58(3):255-67. DOI: 10.1111/j.1600-0897.2007.00511.x. View

17.

Edey L, ODea K, Herbert B, Hua R, Waddington S, MacIntyre D . The Local and Systemic Immune Response to Intrauterine LPS in the Prepartum Mouse. Biol Reprod. 2016; 95(6):125. PMC: 5333944. DOI: 10.1095/biolreprod.116.143289. View

18.

Brown Z, Selke S, Zeh J, Kopelman J, Maslow A, Ashley R . The acquisition of herpes simplex virus during pregnancy. N Engl J Med. 1997; 337(8):509-15. DOI: 10.1056/NEJM199708213370801. View

19.

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. 2003; 28(10):1778-89. DOI: 10.1038/sj.npp.1300248. View

20.

Guo Z, Shi X, Feng Y, Wang B, Feng L, Wang S . Risk factors of HBV intrauterine transmission among HBsAg-positive pregnant women. J Viral Hepat. 2013; 20(5):317-21. PMC: 3623007. DOI: 10.1111/jvh.12032. View