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

Ivan Godinez, Manuela Raffatellu, Hiutung Chu, Tatiane A. Paixão, Takeshi Haneda, Renato L. Santos, Charles L Bevins, Renee M Tsolis, Andreas J Baumler

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)387-398
Number of pages12
JournalInfection and Immunity
Issue number1
StatePublished - Jan 2009

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases


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