title: Roles of interleukin-17 in an experimental Legionella pneumophila pneumonia model.
abstract: Interleukin-17 (IL-17) is a key factor in T helper type 17 (Th17) lineage host responses and plays critical roles in immunological control of a variety of infectious diseases. Although Legionella pneumophila, an intracellular bacterium found widely in the environment, often causes a serious and life-threatening pneumonia in humans, the contribution of IL-17 to immune function during Legionella pneumonia is unknown. In the present study, we used an experimental Legionella pneumonia infection to clarify the role of IL-17 in the resulting immune response. We observed robust production of pulmonary IL-17A and IL-17F (IL-17A/F), peaking on day 1 and declining thereafter. Upregulated production of tumor necrosis factor alpha (TNF-α), IL-6, and IL-1β, but not monocyte chemotactic protein 1 (MCP-1), was observed in Legionella-infected bone marrow-derived macrophages from BALB/c mice that had been stimulated with IL-17A or IL-17F. A significant decrease in the production of proinflammatory cytokines IL-6 and TNF-α was observed in IL-17A/F-deficient mice (BALB/c background) infected with L. pneumophila. Moreover, we found impaired neutrophil migration and lower numbers of chemokines (KC, LIX, and MIP-2) in IL-17A/F-deficient mice. IL-17A/F-deficient mice also eliminated L. pneumophila more slowly and were less likely to survive a lethal challenge. These results demonstrate that IL-17A/F plays a critical role in L. pneumophila pneumonia, probably through induction of proinflammatory cytokines and accumulation of neutrophils at the infection site.
authors.affiliation: Department of Microbiology and Infectious Disease, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kimizuka
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kimura
authors.forename: Tomoo
authors.initials: T
authors.lastname: Saga
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishii
authors.forename: Naoki
authors.initials: N
authors.lastname: Hasegawa
authors.forename: Tomoko
authors.initials: T
authors.lastname: Betsuyaku
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tateda
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000276:immunology*; D016952:Legionella pneumophila / Q000276:immunology* / Q000472:pathogenicity*; D007877:Legionnaires' Disease / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D011014:Pneumonia / Q000276:immunology / Q000382:microbiology / Q000473:pathology
chemical_list: D016207:Cytokines; D020381:Interleukin-17