IL-17D promotes anti-bacterial immunity in Group A Streptococcus infection

Abstract

Abstract Interleukin (IL)-17D is a cytokine in the IL-17 family that is conserved in vertebrates and invertebrates. In contrast to IL-17A, which is expressed in T cells, IL-17D is expressed broadly in non-immune cells. IL-17D can promote immune responses to cancer and viruses in part by inducing chemokines that recruit natural killer cells and neutrophils. Although bacterial infection can induce IL-17D in other species, the role of mammalian IL-17D in anti-bacterial immunity has not been determined. In order to ascertain whether IL-17D has a role in mediating immunity against bacterial infections, we studied intraperitoneal infection by Group A Streptococcus (GAS) S. pyogenes in wild-type (WT) and IL-17D-deficient mice. We found that there was more weight loss and decreased survival in mice deficient in IL-17D compared to WT animals after GAS infection. In addition, IL-17D deficient animals had increased bacterial burden in the kidney and peritoneal cavity after GAS infection compared to WT animals. In WT animals, IL-17D transcript could be induced by GAS infection, correlating with increased levels of the chemokine CCL2 and neutrophil recruitment. Notably, GAS-mediated induction of IL-17D seemed to require live bacteria, indicating that pattern recognition did not mediate induction of IL-17D. Altogether, our results demonstrate a role for IL-17D in sensing replicating bacteria and inducing immune responses important in clearing bacteria in distant organs.