title: Interleukin-17A is required to suppress invasion of Salmonella enterica serovar Typhimurium to enteric mucosa.
abstract: 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.
authors.affiliation: Center of Molecular Biosciences, Tropical Biosphere Research Centre, University of the Ryukyus, Senbaru, Nishihara, Okinawa, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Mayuzumi
authors.forename: Kyoko
authors.initials: K
authors.lastname: Inagaki-Ohara
authors.forename: Catherine
authors.initials: C
authors.lastname: Uyttenhove
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Goro
authors.initials: G
authors.lastname: Matsuzaki
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012485:Salmonella typhi / Q000276:immunology* / Q000472:pathogenicity; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D014435:Typhoid Fever / Q000276:immunology*; D023083:beta-Defensins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; D020381:Interleukin-17; D023083:beta-Defensins; C540070:beta-defensin 3, mouse; D007371:Interferon-gamma