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Title (Primary) 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
Author Schulz, S.M.; Köhler, G.; Schütze, N.; Knauer, J.; Straubinger, R.K.; Chackerian, A.A.; Witte, E.; Wolk, K.; Sabat, R.; Iwakura, Y.; Holscher, C.; Müller, U.; Kastelein, R.A.; Alber, G.;
Journal Journal of Immunology
Year 2008
Department IMMU;
Volume 181
Issue 11
Language englisch;
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-γ 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.
ID 1436
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=1436
Schulz, S.M., Köhler, G., Schütze, N., Knauer, J., Straubinger, R.K., Chackerian, A.A., Witte, E., Wolk, K., Sabat, R., Iwakura, Y., Holscher, C., Müller, U., Kastelein, R.A., Alber, G. (2008):
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
J. Immunol. 181 (11), 7891 - 7901