Interleukin-23 is required for protection against Listeria monocytogenes (133.24)

Abstract

Abstract Listeria monocytogenes (LM) is a gram-positive, intracellular bacterium that can induce spontaneous abortion, septicemia, and meningitis. Recently, it has been demonstrated that interleukin (IL)-17A is necessary for an optimal immune response against LM in the liver. As IL-23-dependent cytokines, IL-17A and IL-17F induce the mobilization of neutrophils to sites of infection. The importance of IL-23 during infection with LM has not been studied. We demonstrate here that IL-23 and the IL-17 receptor A (IL-17RA), which mediates both IL-17A and IL-17F signaling, are necessary for resistance against LM infection. During infection with LM, mice deficient in either IL-23 (IL-23p19 KO) or the IL-17RA (IL-17RA KO) have increased susceptibility to infection and increased bacterial burden in the spleen and liver. Interestingly, IL-17A, IL-17F, and IL-22 are decreased in supernatants from cells of LM infected IL-23p19 KO mice. Furthermore, neutrophils are decreased in IL-23p19 KO and IL-17RA KO mice at early time points. When IL-23p19 KO mice are rescued with the administration of exogenous IL-17A, a protective phenotype similar to that seen during infection of wild-type mice is achieved. Therefore, it is likely that IL-23 regulates the optimal production of IL-17A/F during LM infection which results in early neutrophil recruitment and bacterial clearance.