title: Alveolar macrophages and neutrophils are the primary reservoirs for Legionella pneumophila and mediate cytosolic surveillance of type IV secretion.
abstract: Legionella pneumophila, an intracellular pathogen responsible for the severe pneumonia Legionnaires' disease, uses its dot/icm-encoded type IV secretion system (T4SS) to translocate effector proteins that promote its survival and replication into the host cell cytosol. However, by introducing bacterial products into the host cytosol, L. pneumophila also activates cytosolic immunosurveillance pathways, thereby triggering robust proinflammatory responses that mediate the control of infection. Thus, the pulmonary cell types that L. pneumophila infects not only may act as an intracellular niche that facilitates its pathogenesis but also may contribute to the immune response against L. pneumophila. The identity of these host cells remains poorly understood. Here, we developed a strain of L. pneumophila producing a fusion protein consisting of β-lactamase fused to the T4SS-translocated effector RalF, which allowed us to track cells injected by the T4SS. Our data reveal that alveolar macrophages and neutrophils both are the primary recipients of T4SS-translocated effectors and harbor viable L. pneumophila during pulmonary infection of mice. Moreover, both alveolar macrophages and neutrophils from infected mice produced tumor necrosis factor and interleukin-1α in response to T4SS-sufficient, but not T4SS-deficient, L. pneumophila. Collectively, our data suggest that alveolar macrophages and neutrophils are both an intracellular reservoir for L. pneumophila and a source of proinflammatory cytokines that contribute to the host immune response against L. pneumophila during pulmonary infection.
authors.affiliation: Immunology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Copenhaver
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Cierra N
authors.initials: CN
authors.lastname: Casson
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Hieu T
authors.initials: HT
authors.lastname: Nguyen
authors.affiliation: Immunology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Fung
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Duda
authors.affiliation: Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Roy
authors.affiliation: Immunology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA sunshin@mail.med.upenn.edu.
authors.forename: Sunny
authors.initials: S
authors.lastname: Shin
mesh_terms: D000818:Animals; D058947:Bacterial Secretion Systems; D003600:Cytosol / Q000378:metabolism / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D054884:Host-Pathogen Interactions; D053582:Interleukin-1alpha / Q000378:metabolism; D016952:Legionella pneumophila / Q000276:immunology* / Q000502:physiology*; D007877:Legionnaires' Disease / Q000276:immunology / Q000382:microbiology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D058947:Bacterial Secretion Systems; D053582:Interleukin-1alpha; D014409:Tumor Necrosis Factor-alpha
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