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Modulation of Th17 and regulatory T‐cell responses during murine pregnancy contributes to increased maternal susceptibility to Salmonella Typhimurium infection
Author(s) -
Agbayani Gerard,
Wachholz Kristina,
Chattopadhyay Anindita,
Gurnani Komal,
Murphy Shawn P.,
Krishnan Lakshmi
Publication year - 2017
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12742
Subject(s) - immunology , pregnancy , spleen , exacerbation , in vivo , downregulation and upregulation , inflammation , interleukin 17 , blockade , tumor necrosis factor alpha , placenta , ex vivo , medicine , fetus , biology , receptor , biochemistry , genetics , microbiology and biotechnology , gene
Problem Salmonella Typhimurium ( S . Tm) infection in pregnant mice results in massive placental infection, fetal loss, and exacerbated systemic infection. The Th17 host response can aid control of S . Tm infection, whereas successful pregnancy correlates to a dampened inflammatory and enhanced regulatory T‐cell (Treg) response. Method of study Mice were infected systemically with S . Tm and tissue bacterial burden, splenic Th17 and Treg cell numbers, and serum cytokines were analyzed. Splenic and/or placental mRNA expression of IL ‐17A, ROR γ‐t, IL ‐10, and TNF was determined. The effects of in vivo CD 25 + cell depletion and TLR 4 blockade on the course of S . Tm infection and Th17 response were determined. Results Enhanced S . Tm burden in pregnant mice was associated with time‐dependent increased serum inflammatory cytokines. In vivo, TLR 4 blockade reduced splenic S . Tm burden, suggesting detrimental TLR 4‐mediated inflammation. However, the splenic and placental Th17 response was reduced in S . Tm‐infected pregnant mice relative to non‐pregnant controls. Alternatively, there was an increase in splenic Treg frequency in pregnant mice and depletion of this subset reduced bacterial burden and increased the Th17 response. Conclusion Downregulation of Th17 cell responses by Tregs during pregnancy potentially contributes to exacerbation of S . Tm infection in pregnant mice.