title: Nonhematopoietic cells are key players in innate control of bacterial airway infection.
abstract: Airborne pathogens encounter several hurdles during host invasion, including alveolar macrophages (AMs) and airway epithelial cells (AECs) and their products. Although growing evidence indicates pathogen-sensing capacities of epithelial cells, the relative contribution of hematopoietic versus nonhematopoietic cells in the induction of an inflammatory response and their possible interplay is still poorly defined in vivo in the context of infections with pathogenic microorganisms. In this study, we show that nonhematopoietic cells, including AECs, are critical players in the inflammatory process induced upon airway infection with Legionella pneumophila, and that they are essential for control of bacterial infections. Lung parenchymal cells, including AECs, are not infected themselves by L. pneumophila in vivo but rather act as sensors and amplifiers of inflammatory cues delivered by L. pneumophila-infected AM. We identified AM-derived IL-1β as the critical mediator to induce chemokine production in nonhematopoietic cells in the lung, resulting in swift and robust recruitment of infection-controlling neutrophils into the airways. These data add a new level of complexity to the coordination of the innate immune response to L. pneumophila and illustrate how the cross talk between leukocytes and nonhematopoietic cells contributes to efficient host protection.
authors.affiliation: Institute of Microbiology, Swiss Federal Institute of Technology Zurich, 8093 Zurich, Switzerland.
authors.forename: Salomé
authors.initials: S
authors.lastname: LeibundGut-Landmann
authors.forename: Kerstin
authors.initials: K
authors.lastname: Weidner
authors.forename: Hubert
authors.initials: H
authors.lastname: Hilbi
authors.forename: Annette
authors.initials: A
authors.lastname: Oxenius
mesh_terms: D000818:Animals; D058947:Bacterial Secretion Systems / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000502:physiology; D016952:Legionella pneumophila / Q000276:immunology; D007877:Legionnaires' Disease / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D011828:Radiation Chimera; D020545:Respiratory Mucosa / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*
chemical_list: D058947:Bacterial Secretion Systems; D018836:Inflammation Mediators; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88