Foxp3 + regulatory T cell expansion required for sustaining pregnancy compromises host defense against prenatal bacterial pathogens

Jared H. Rowe, James M. Ertelt, Marijo N. Aguilera, Michael A Farrar, Sing Sing Way

Research output: Contribution to journalArticlepeer-review

111 Scopus citations

Abstract

Although pregnancy confers unique susceptibility to infection, the pregnancy-associated immune defects that erode host defense remain largely undefined. Herein, we demonstrate that expansion of immune-suppressive Foxp3 + regulatory T cells (Tregs) which occurs physiologically during pregnancy or when experimentally induced in transgenic mice caused enhanced susceptibility to prenatal pathogens including Listeria and Salmonella species. Reciprocally, infection susceptibility was uniformly reduced with Treg ablation. Importantly however, the sustained expansion of maternal Tregs was essential for maintaining immune tolerance to the developing fetus because even partial transient ablation of Foxp3-expressing cells fractured maternal tolerance to fetal antigen and triggered fetal resorption. Interestingly, Foxp3 cell-intrinsic defects in the immune-suppressive cytokine IL-10 alone were sufficient to override Treg-mediated infection susceptibility, while IL-10 was nonessential for sustaining pregnancy. Thus, maternal Treg expansion required for sustaining pregnancy creates naturally occurring holes in host defense that confer prenatal infection susceptibility.

Original languageEnglish (US)
Pages (from-to)54-64
Number of pages11
JournalCell Host and Microbe
Volume10
Issue number1
DOIs
StatePublished - Jul 21 2011

Bibliographical note

Funding Information:
We thank Dr. Alexander Rudensky for providing Foxp3 DTR and Foxp3 GFP mice; Dr. Marc Jenkins for providing Actin-OVA mice; Dr. Daniel Mueller for providing CTLA-4-deficient mice; Drs. Michael Bevan, Bryce Binstadt, Bruce Blazar, Kristen Hogquist, Stephen McSorley, Matthew Mescher, Joseph Sun, and Viava Vezys for helpful discussions; and Sandra Horn and the University of Minnesota Mouse Genetics Laboratory for assistance in synchronized mouse breeding. This research was supported by National Institutes of Health grants F30-DK084674 (J.H.R.) and R01-AI087830 (S.S.W.).

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