International Immunology Advance Access originally published online on March 18, 2009
International Immunology 2009 21(5):555-565; doi:10.1093/intimm/dxp025
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Differential IL-23 requirement for IL-22 and IL-17A production during innate immunity against Salmonella enterica serovar Enteritidis
1 Institute of Immunology, College of Veterinary Medicine, An den Tierkliniken 11, 04103 Leipzig, Germany
2 Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, University Hospital Charité, Campus-Charité Mitte, Charitéplatz 1, 10117 Berlin, Germany
3 Biomedical-Biotechnological Center, University of Leipzig, An den Tierkliniken 11, 04103 Leipzig, Germany
4 Present address: Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität Munich, Veterinärstraβe 13, 80539 Munich, Germany
Correspondence to: G. Alber; E-mail: alber{at}vetmed.uni-leipzig.de
Early activation of the IL-12/IFN-
axis has been shown following Salmonella enterica serovar Enteritidis (S. Enteritidis) infection. We were interested to study whether IL-22 and IL-17A production is initiated early in response to S. Enteritidis. We demonstrate here that IL-22 was strongly elevated in the peritoneal lavage fluid and in serum already 1 day post-intraperitoneal infection (d.p.i.) of mice; not only IL-22 but also IL-17A was produced ex vivo by activated peritoneal exudate cells (PEC). Peritoneal 
T cells were identified as cellular source of IL-17A. The early IL-22 production was completely IL-23-dependent. In contrast, IL-17A production was only partially IL-23-dependent. To investigate the local production of upstream cytokines important for induction of IL-22, IL-17A and IFN- during salmonellosis, the production of IL-23 and IL-12 was studied. Elevated p19 and p40 mRNA levels were found in PEC at 1 d.p.i., whereas p35 mRNA levels were not changed. Besides, the Th17-promoting cytokines IL-6, IL-1β and transforming growth factor-β were produced in response to S. Enteritidis. However, IL-6 was not required for IL-22 or IL-17A production by PEC. By ex vivo analysis of PEC at 1 d.p.i., we show that the major producers of early IL-12/23p40 in the peritoneal cavity were dendritic cells (DC), whereas macrophages notably contributed to IL-6 production. Taken together, these data suggest that DC initiate early IL-22 production at the site of infection which may contribute to resistance against salmonellosis. Furthermore, we provide evidence that production of IL-22 and IL-17A is differentially regulated during infection.
Keywords: cytokine, dendritic cell, IL-12 family, IL-22 release, macrophage
* These authors contributed equally to this work.
Received 13 June 2008, accepted 14 February 2009.
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