Interleukin‐17A is required to suppress invasion of Salmonella enterica serovar Typhimurium to enteric mucosa

Abstract

Summary Salmonella enterica serovar Typhimurium (S. typhimurium) causes a localized enteric infection and its elimination is dependent on a T helper type 1 immune response. However, the mechanism of the protective immune response against the pathogen in gut‐associated lymphoid tissue (GALT) at an early stage of the infection is not yet clarified. Here, we show that interleukin‐17A (IL‐17A) was constitutively expressed in GALT; it was also detected on crypt and epithelial cells of the small intestine. Neutralization of the IL‐17A in the intestinal lumen exacerbated epithelial damage induced by intestinal S. typhimurium infection at an early stage of the infection. The result suggests that IL‐17A has a pivotal role in the immediate early stage of protection against bacterial infection at the intestinal mucosa. As IL‐17A neutralization also suppressed the constitutive localization of β‐defensin 3 (BD3), an IL‐17A‐induced antimicrobial peptide, at the apical site of the intestinal mucosa, it is estimated that IL‐17A constitutively induces the expression of the antimicrobial peptide to kill invading pathogens at the epithelial surface immediately after the infection. In contrast, interferon‐γ is induced around 3 days after S. typhimurium infection, and its expression level increases thereafter. Taken together, the findings lead to the hypothesis that IL‐17A participates in the immediate early stage of protection against S. typhimurium intestinal infection whereas interferon‐γ is important at a later stage of the infection.

The Polysaccharide Capsule of Campylobacter jejuni Modulates the Host Immune Response

“…IL-22 exerts its protective effects by inducing epithelial cells to produce antibacterial molecules (37). Recently, Th17 responses have been demonstrated to have protective roles against Salmonella and Citrobacter infections in mice (29,30). To date, only limited data exist regarding Th17 responses and Campylobacter infection.…”

“…These models can be exploited to evaluate innate or adaptive Th17 responses. Whereas iTh17 responses can be induced relatively quickly by cytokine signals (29,30), adaptive Th17 responses occur later (days to weeks) (34) and are antigenspecific responses. In our present study, the Th17 responses likely represented an adaptive immune response, since Jackson Laboratory mice were used.…”

“…LPLs were restimulated in vitro with PMA (20 ng/ml) and ionomycin (500 ng/ml) for 4 to 6 h. Protein transport was inhibited by addition of brefeldin A (10 g/ml). T helper 17 (Th17) responses have come into focus due to their roles in maintaining intestinal homeostasis (27,28) and protective immune responses against enteric pathogens (28)(29)(30)(31). The gut Th17 response is composed of both innate and adaptive immune system components.…”

CD4+T Cells: Guardians of the Phagosome

“…Indeed, it was reported that mice lacking the IL-17 receptor were defective in the long-term control of M. tuberculosis infection (156). On the other hand, M. tuberculosis and Salmonella infections are controlled normally in IL-23-deficient mice, in which Th17 generation does not occur (157,158), and neutralization of IL-17 had no effect on the control of L. major infection (159). Furthermore, people with mutations that affect the expression of IL-17 or IL-17 receptor are susceptible to Candida and Staphylococcus aureus skin infections (160) but do not appear to be susceptible to the phagosomal pathogens that afflict people lacking CD4 ϩ T cells or IL-12 receptor (27,28,161).…”

Human T h 17 Cells Lack HIV-Inhibitory RNases and Are Highly Permissive to Productive HIV Infection

“…The early loss of the enterocyte-proliferative and antimicrobial peptide-inducing cytokines produced by T h 17 cells impairs the integrity of the gut mucosal barrier, driving microbial translocation and chronic immune activation-key determinants of disease progression to AIDS (25,26).…”