Interleukin-23 orchestrates mucosal responses to Salmonella enterica serotype Typhimurium in the intestine

Infect Immun. 2009 Jan;77(1):387-98. doi: 10.1128/IAI.00933-08. Epub 2008 Oct 27.


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-gamma), interleukin-22 (IL-22), and IL-17 expression (genes Ifn-gamma, 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-gamma 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 alphabeta 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 gammadelta T cells was observed in the lamina propria during serotype Typhimurium infection. Compared to wild-type mice, gammadelta T-cell-receptor-deficient mice exhibited blunted expression of IL-17 during serotype Typhimurium infection, while IFN-gamma expression was normal. These data suggested that gammadelta 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD3 Complex / analysis
  • Cecum / immunology
  • Cytokines / biosynthesis
  • Flow Cytometry
  • Gene Expression Profiling
  • Interleukin-23 / deficiency
  • Interleukin-23 / immunology*
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / pathology
  • Lymphocyte Subsets / chemistry
  • Lymphocyte Subsets / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Interleukin / analysis
  • Salmonella typhimurium / immunology*


  • CD3 Complex
  • Cytokines
  • Interleukin-23
  • Receptors, Interleukin