title: Endogenous IL-17 as a factor determining the severity of Clostridium difficile infection in mice.
abstract: Clostridium difficile infection (CDI) is a toxin-mediated intestinal disease. Toxin A, toxin B and binary toxin are believed to be responsible for the pathogenesis of CDI, which is characterized by massive infiltration of neutrophils at the infected intestinal mucosa. IL-17 is one of the cytokines that play critical roles in several inflammatory and immunological diseases through various actions, including promoting neutrophil recruitment. The aim of this study was to examine the role of this cytokine in CDI by employing IL-17 A and F double knockout (IL-17 KO) mice for the CDI model. We demonstrated that IL-17 KO mice were more resistant to CDI than WT mice using several factors, such as diarrhoea score, weight change and survival rate. Although the bacterial numbers of C. difficile in faeces were not different, the inflammatory mediator levels at the large intestine on day 3 post-infection were attenuated in IL-17 KO mice. Finally, we showed that infiltration of neutrophils, but not macrophages, in the large intestine was significantly decreased in IL-17 KO mice compared to WT mice. In conclusion, the data demonstrate that endogenous IL-17 may be a factor determining the severity of CDI in mice. Although the mechanism is totally unknown, IL-17-mediated inflammatory responses, such as cytokine/chemokine production and neutrophil accumulation, may be plausible targets for future investigations.
authors.affiliation: Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo, Japan.|Division of Pediatrics, Toho University Omori Medical Center, Tokyo, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Mori
authors.affiliation: Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kajiwara
authors.affiliation: Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kimura
authors.affiliation: Division of Chronic Inflammatory Diseases, Advanced Medical Research Center, Toho University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yoshikiyo
authors.initials: Y
authors.lastname: Akasaka
authors.affiliation: Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ishii
authors.affiliation: Division of Pediatrics, Toho University Omori Medical Center, Tokyo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Saji
authors.affiliation: Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tateda
mesh_terms: D000818:Animals; D001835:Body Weight; D002465:Cell Movement; D016360:Clostridioides difficile / Q000276:immunology* / Q000472:pathogenicity*; D003967:Diarrhea / Q000473:pathology; D004195:Disease Models, Animal; D004761:Enterocolitis, Pseudomembranous / Q000473:pathology*; D020381:Interleukin-17 / Q000172:deficiency / Q000378:metabolism*; D007420:Intestine, Large / Q000473:pathology; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D012720:Severity of Illness Index; D016019:Survival Analysis
chemical_list: D020381:Interleukin-17