Interleukin-23 Orchestrates Mucosal Responses to Salmonella enterica Serotype Typhimurium in the Intestine

• Published in: Infection and Immunity 2009-01, Vol.77 (1), p.387-398
• Main Authors: Godinez, Ivan, Raffatellu, Manuela, Chu, Hiutung, Paixão, Tatiane A, Haneda, Takeshi, Santos, Renato L, Bevins, Charles L, Tsolis, Renée M, Bäumler, Andreas J
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Bacteriology; Biological and medical sciences; CD3 antigen; CD3 Complex - analysis; Cecum; Cecum - immunology; Cytokines - biosynthesis; Data processing; Flow Cytometry; Fundamental and applied biological sciences. Psychology; g-Interferon; Gene Expression Profiling; Host Response and Inflammation; Infection; Inflammation; Interferon; Interleukin 17; Interleukin 22; Interleukin 23; Interleukin-23 - deficiency; Interleukin-23 - immunology; Intestinal Mucosa - immunology; Intestinal Mucosa - pathology; Intestine; lamina propria; Leukocytes (neutrophilic); Lymphocyte Subsets - chemistry; Lymphocyte Subsets - immunology; Lymphocytes T; Mice; Mice, Inbred C57BL; Mice, Knockout; Microbiology; Miscellaneous; Mucosa; Receptors, Interleukin - analysis; Salmonella enterica; Salmonella typhimurium - immunology; Serotypes
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00933-08

Salmonella enterica serotype Typhimurium causes an acute inflammatory reaction in the ceca of streptomycin-pretreated mice that involves T-cell-dependent induction of gamma interferon (IFN-γ), interleukin-22 (IL-22), and IL-17 expression (genes Ifn-γ, Il-22, and Il-17, respectively). We investigated here the role of IL-23 in initiating these inflammatory responses using the streptomycin-pretreated mouse model. Compared to wild-type mice, the expression of IL-17 was abrogated, IL-22 expression was markedly reduced, but IFN-γ expression was normal in the ceca of IL-23p19-deficient mice during serotype Typhimurium infection. IL-23p19-deficient mice also exhibited a markedly reduced expression of regenerating islet-derived 3 gamma, keratinocyte-derived cytokine, and reduced neutrophil recruitment into the cecal mucosa during infection. Analysis of CD3⁺ lymphocytes in the intestinal mucosa by flow cytometry revealed that αβ T cells were the predominant cell type expressing the IL-23 receptor in naive mice. However, a marked increase in the number of IL-23 receptor-expressing γδ T cells was observed in the lamina propria during serotype Typhimurium infection. Compared to wild-type mice, γδ T-cell-receptor-deficient mice exhibited blunted expression of IL-17 during serotype Typhimurium infection, while IFN-γ expression was normal. These data suggested that γδ T cells are a significant source, but not the sole source, of IL-17 in the acutely inflamed cecal mucosa of mice. Collectively, our results point to IL-23 as an important player in initiating a T-cell-dependent amplification of inflammatory responses in the intestinal mucosa during serotype Typhimurium infection.