title: Interleukin 1 receptor-driven neutrophil recruitment accounts to MyD88-dependent pulmonary clearance of legionella pneumophila infection in vivo.
abstract: Legionella pneumophila, the etiological agent of Legionnaires' disease, triggers activation of multiple innate immune pathways that lead to the restriction of bacterial replication in vivo. Despite the critical role for MyD88 in infection clearance, the receptors and mechanisms responsible for MyD88-mediated pulmonary bacterial clearance are still unclear. Here, we used flagellin mutants of L. pneumophila, which bypass the NAIP5/NLRC4-mediated restriction of bacterial replication, to assess the receptors involved in MyD88-mediated pulmonary bacterial clearance. By systematically comparing pulmonary clearance of L. pneumophila in C57BL/6 MyD88(-/-), TLR2(-/-), TLR3(-/-), TLR4(-/-), TLR9(-/-), IL-1R(-/-), and IL-18(-/-) mice, we found that, while the knockout of a single Toll-like receptor or interleukin 18 resulted only in minor impairment of bacterial clearance, deficiency in the interleukin 1 (IL-1) receptor led to a significant impairment. IL-1/MyD88-mediated pulmonary bacterial clearance occurs via processes involving the recruitment of neutrophils. Collectively, our data contribute to the understanding of the effector mechanisms involved in MyD88-mediated pulmonary bacterial clearance.
authors.affiliation: Department of Cell Biology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
authors.forename: Danielle P A
authors.initials: DP
authors.lastname: Mascarenhas
authors.affiliation: Department of Cell Biology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
authors.forename: Marcelo S F
authors.initials: MS
authors.lastname: Pereira
authors.affiliation: Department of Cell Biology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
authors.forename: Graziele Z
authors.initials: GZ
authors.lastname: Manin
authors.affiliation: Department of Cell Biology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
authors.forename: Juliana I
authors.initials: JI
authors.lastname: Hori
authors.affiliation: Department of Cell Biology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
authors.forename: Dario S
authors.initials: DS
authors.lastname: Zamboni
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D016952:Legionella pneumophila / Q000276:immunology*; D007877:Legionnaires' Disease / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D020556:Neutrophil Infiltration; D017472:Receptors, Interleukin-1 / Q000378:metabolism*
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D017472:Receptors, Interleukin-1
keywords: IL-1 receptor; Legionella pneumophila; MyD88; neutrophils; pulmonary bacterial clearance