Regulatory T cells and the immune pathogenesis of prenatal infection.
Pregnancy in placental mammals offers exceptional comprehensive benefits of in utero protection, nutrition, and metabolic waste elimination for the developing fetus. However, these benefits also require durable strategies to mitigate maternal rejection of fetal tissues expressing foreign paternal antigens. Since the initial postulate of expanded maternal immune tolerance by Sir Peter Medawar 60 years ago, an amazingly elaborate assortment of molecular and cellular modifications acting both locally at the maternal-placental interface and systemically have been shown to silence potentially detrimental maternal immune responses. In turn, simultaneously maintaining host defense against the infinite array of potential pathogens during pregnancy is equally important. Fortunately, resistance against most infections is preserved seamlessly throughout gestation. On the other hand, recent studies on pathogens with unique predisposition for prenatal infections have uncovered distinctive holes in host defense associated with the reproductive process. Using these infections to probe the response during pregnancy, the immune suppressive regulatory subset of maternal CD4 T cells has been increasingly shown to dictate the inter-workings between prenatal infection susceptibility and pathogenesis of ensuing pregnancy complications. Herein, the recent literature suggesting a necessity for maternal regulatory T cells (Tregs) in pregnancy-induced immunological shifts that sustain fetal tolerance is reviewed. Additional discussion is focused on how expansion of maternal Treg suppression may become exploited by pathogens that cause prenatal infections and the perilous potential of infection-induced immune activation that may mitigate fetal tolerance and inadvertently inject hostility into the protective in utero environment.
Division of Infectious Diseases, Cincinnati Children's Hospital, 3333 Burnet Avenue, MLC 7017, Cincinnati, Ohio 45229, USA.
Jared H
JH
Rowe
James M
JM
Ertelt
Lijun
L
Xin
Sing Sing
SS
Way
D005260:Female; D005315:Fetal Diseases / Q000276:immunology; D005333:Fetus / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007113:Immunity, Innate / Q000502:physiology; D011247:Pregnancy / Q000276:immunology*; D011251:Pregnancy Complications, Infectious / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*