International Immunology Advance Access published online on July 3, 2008
International Immunology, doi:10.1093/intimm/dxn069
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IL-17A is produced by Th17, 
T cells and other CD4– lymphocytes during infection with Salmonella enterica serovar Enteritidis and has a mild effect in bacterial clearance
1 Institute of Immunology, College of Veterinary Medicine, University of Leipzig, An den Tierkliniken 11, 04103 Leipzig, Germany
2 Gerhard Domagk Institute of Pathology, University of Münster, Gerhard-Domagk-Str. 17, 48149 Münster, Germany
3 Research Center Borstel, Parkallee 22, 23845 Borstel, Germany
4 Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
Correspondence to: Correspondence to: G. Alber; E-mail: alber{at}rz.uni-leipzig.de
Th17 cells represent a new pro-inflammatory Th cell lineage distinct from Th1 and Th2 cells. Th17 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–/– 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–/– mice as compared with WT mice. Overall, IL-17A–/– 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+ Th17 cells developed upon infection with Salmonella. CD4– 
TCR+ and CD4– TCR– cells were found to be additional IL-17A-producing cell populations. In infected IL-17A–/– mice, a normal Th1 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- axis which is essential for protective immunity against salmonellosis in mice and men.
Keywords: bacteria, cytokine, DTH, mouse, T cell
Transmitting editor: T. Hirano
Received 29 February 2008, accepted 3 June 2008.
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