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Protective immunity to systemic infection with attenuated Salmonella enterica serovar enteritidis in the absence of IL-12 is associated with IL-23-dependent IL-22, but not IL-17.

Abstract
IL-12 is essential for protective T cell-mediated immunity against Salmonella infection. To characterize the role of the related cytokine IL-23, wild-type (WT) C57BL/6 and p19(-/-) mice were infected systemically with an attenuated strain of Salmonella enterica serovar Enteritidis (S. Enteritidis). IL-23-deficient mice controlled infection with S. Enteritidis similarly as WT mice. Similar IFN-gamma production as compared with WT mice, but defective IL-17A and IL-22 production was found in the absence of IL-23. Nevertheless, although IL-23 is required for T cell-dependent cytokine responses, IL-23 is dispensable for protection against S. Enteritidis when IL-12 is present. To analyze the role of IL-23 in the absence of IL-12, low doses of S. Enteritidis were administered to p35(-/-) mice (lacking IL-12), p35/19(-/-) mice (lacking IL-12 and IL-23), p35/40(-/-) mice (lacking IL-12, IL-23, and homodimeric IL-12p40), or p35/IL-17A(-/-) mice (lacking IL-12 and IL-17A). We found survival of p35(-/-) and p35/IL-17A(-/-) mice, whereas p35/19(-/-) and p35/40(-/-) mice died within 3-6 wk and developed liver necrosis. This indicates that IL-23, but not homodimeric IL-12p40, is required for protection, which, surprisingly, is independent of IL-17A. Moreover, protection was associated with IL-22, but not IL-17F or IL-21 expression or with neutrophil recruitment. Finally, anti-IL-22 treatment of S. Enteritidis-infected p35(-/-) mice resulted in liver necrosis, indicating a central role of IL-22 in hepatocyte protection during salmonellosis. In conclusion, IL-23-dependent IL-22, but not IL-17 production is associated with protection against systemic infection with S. Enteritidis in the absence of IL-12.
AuthorsSilke M Schulz, Gabriele Köhler, Nicole Schütze, Jens Knauer, Reinhard K Straubinger, Alissa A Chackerian, Ellen Witte, Kerstin Wolk, Robert Sabat, Yoichiro Iwakura, Christoph Holscher, Uwe Müller, Robert A Kastelein, Gottfried Alber
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 181 Issue 11 Pg. 7891-901 (Dec 01 2008) ISSN: 1550-6606 [Electronic] United States
PMID19017979 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Interleukin-12 Subunit p40
  • Interleukin-17
  • Interleukin-23
  • Interleukins
  • Interferon-gamma
  • interleukin-22
Topics
  • Animals
  • Female
  • Hepatocytes (immunology)
  • Interferon-gamma (genetics, immunology)
  • Interleukin-12 Subunit p40 (genetics, immunology)
  • Interleukin-17 (genetics, immunology)
  • Interleukin-23 (genetics, immunology)
  • Interleukins (genetics, immunology)
  • Liver (immunology)
  • Mice
  • Mice, Knockout
  • Necrosis (genetics, immunology)
  • Neutrophils (immunology)
  • Salmonella Infections (genetics, immunology)
  • Salmonella enteritidis (immunology)

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