IL-17A is produced by T sub(h)17, gamma delta T cells and other CD4 super(-) lymphocytes during infection with Salmonella enterica serovar Enteritidis and has a mild effect in bacterial clearance

T sub(h)17 cells represent a new pro-inflammatory T sub(h) cell lineage distinct from T sub(h)1 and T sub(h)2 cells. T sub(h)17 cells have been shown to be involved in extracellular bacterial infection but their role in intracellular infection remains unclear. We found antigen-specific IL-17A production during a systemic infection of mice with the facultative intracellular bacterium Salmonella enterica serovar Enteritidis (S. Enteritidis) and examined the function and cellular source of IL-17A during the adaptive immune response to S. Enteritidis. Infected IL-17A super(-/-) mice survived completely after inoculation with the highest infection dose found to be sub-lethal for wild-type (WT) C57BL/6 mice. However, at 20 and 80 days post-infection (d.p.i.), we repeatedly found mildly elevated bacterial burden in spleen and liver of IL-17A super(-/-) mice as compared with WT mice. Overall, IL-17A super(-/-) mice showed reduced clearance of S. Enteritidis. S. Enteritidis-specific IL-17A production was induced in splenocytes and lymph node cells of infected WT mice at both time points, 20 and 80 d.p.i. Classical CD4 super(+) T sub(h)17 cells developed upon infection with SALMONELLA: CD4 super(-) gamma delta TCR super(+) and CD4 super(-) gamma delta TCR super(-) cells were found to be additional IL-17A-producing cell populations. In infected IL-17A super(-/-) mice, a normal T sub(h)1 cytokine profile was observed consistent with the overall subtle phenotype. Nevertheless, in the absence of IL-17A, recruitment of neutrophils and delayed-type hypersensitivity (DTH) reactivity was significantly compromised. Our data indicate that IL-17A responses are induced by Salmonella and mildly contribute to protective immunity during S. Enteritidis infection. Thus, IL-17A complements the IL-12/IFN- gamma axis which is essential for protective immunity against salmonellosis in mice and men.