Modulation of Th17 and regulatory T-cell responses during murine pregnancy contributes to increased maternal susceptibility to Salmonella Typhimurium infection
Gerard Agbayani
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada
Division of Life Sciences, Human Health Therapeutics, National Research Council Canada, Ottawa, ON, Canada
Search for more papers by this authorKristina Wachholz
Division of Life Sciences, Human Health Therapeutics, National Research Council Canada, Ottawa, ON, Canada
Search for more papers by this authorAnindita Chattopadhyay
Division of Life Sciences, Human Health Therapeutics, National Research Council Canada, Ottawa, ON, Canada
Search for more papers by this authorKomal Gurnani
Division of Life Sciences, Human Health Therapeutics, National Research Council Canada, Ottawa, ON, Canada
Search for more papers by this authorShawn P. Murphy
Department of Obstetrics and Gynecology, University of Rochester, Rochester, NY, USA
Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA
Search for more papers by this authorCorresponding Author
Lakshmi Krishnan
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada
Division of Life Sciences, Human Health Therapeutics, National Research Council Canada, Ottawa, ON, Canada
Correspondence
Lakshmi Krishnan, 1200 Montreal Road, M-54, Room 124, Ottawa, ON K1A 0R6, Canada.
Email: [email protected]
Search for more papers by this authorGerard Agbayani
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada
Division of Life Sciences, Human Health Therapeutics, National Research Council Canada, Ottawa, ON, Canada
Search for more papers by this authorKristina Wachholz
Division of Life Sciences, Human Health Therapeutics, National Research Council Canada, Ottawa, ON, Canada
Search for more papers by this authorAnindita Chattopadhyay
Division of Life Sciences, Human Health Therapeutics, National Research Council Canada, Ottawa, ON, Canada
Search for more papers by this authorKomal Gurnani
Division of Life Sciences, Human Health Therapeutics, National Research Council Canada, Ottawa, ON, Canada
Search for more papers by this authorShawn P. Murphy
Department of Obstetrics and Gynecology, University of Rochester, Rochester, NY, USA
Department of Microbiology and Immunology, University of Rochester, Rochester, NY, USA
Search for more papers by this authorCorresponding Author
Lakshmi Krishnan
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada
Division of Life Sciences, Human Health Therapeutics, National Research Council Canada, Ottawa, ON, Canada
Correspondence
Lakshmi Krishnan, 1200 Montreal Road, M-54, Room 124, Ottawa, ON K1A 0R6, Canada.
Email: [email protected]
Search for more papers by this authorAbstract
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, RORγ-t, IL-10, and TNF was determined. The effects of in vivo CD25+ cell depletion and TLR4 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, TLR4 blockade reduced splenic S. Tm burden, suggesting detrimental TLR4-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.
Supporting Information
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