title: Role of Toll-like receptor 2 in recognition of Legionella pneumophila in a murine pneumonia model.
abstract: Legionella pneumophila is an intracellular organism and the major aetiological agent of Legionnaires' disease. Although recent progress has identified Toll-like receptors (TLRs) as receptors for recognition of pathogen-associated molecular patterns in a variety of micro-organisms, understanding the contribution of TLRs to the host response in L. pneumophila infection is still limited. This study examined the roles of TLR2 and TLR4 in murine L. pneumophila pneumonia and an in vitro infection model using bone-marrow-derived macrophages. TLR2-deficient mice, but not TLR4-deficient mice, demonstrated higher lethal sensitivity to pulmonary challenge with L. pneumophila than wild-type mice (P<0.05). Although no differences in pulmonary bacterial burden were observed among the mouse strains examined, lower values of macrophage inflammatory protein-2 (MIP-2), keratinocyte-derived cytokine and interleukin (IL)-6 and higher IL-12 levels were noted in lung homogenates of TLR2-deficient mice compared with the wild-type control and TLR4-deficient mice. Recruitment of inflammatory cells, particularly neutrophils, was severely disturbed in the lungs of TLR2-deficient mice. Reduced MIP-2 production was demonstrated in bone-marrow-derived macrophages from TLR2-deficient mice in response to live L. pneumophila and purified LPS of this strain, but not Escherichia coli LPS. These data highlight the involvement and importance of TLR2 in the pathogenesis of L. pneumophila pneumonia in mice. The results showed that TLR2-mediated recognition of Legionella LPS and subsequent chemokine-dependent cellular recruitment may be a crucial host innate response in L. pneumophila pneumonia.
authors.affiliation: Fourth Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.|Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo 143-8540, Japan.
authors.forename: Etsu T
authors.initials: ET
authors.lastname: Fuse
authors.affiliation: Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo 143-8540, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tateda
authors.affiliation: Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo 143-8540, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kikuchi
authors.affiliation: Department of Microbiology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Denkaseiken Co. Ltd, Gosenshi, Minami-motomachi 1-2-2, Niigata, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Gondaira
authors.affiliation: Fourth Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Arata
authors.initials: A
authors.lastname: Azuma
authors.affiliation: Fourth Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Kudoh
authors.affiliation: Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0360, USA.
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Standiford
authors.affiliation: Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo 143-8540, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D054426:Chemokine CXCL2; D004195:Disease Models, Animal; D007113:Immunity, Innate; D018664:Interleukin-12 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D016952:Legionella pneumophila / Q000235:genetics / Q000276:immunology*; D007877:Legionnaires' Disease / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015846:Monokines / Q000032:analysis; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology
chemical_list: D054426:Chemokine CXCL2; D015850:Interleukin-6; D008070:Lipopolysaccharides; D015846:Monokines; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D018664:Interleukin-12