title: Pneumolysin expression by streptococcus pneumoniae protects colonized mice from influenza virus-induced disease.
abstract: The response to influenza virus (IAV) infection and severity of disease is highly variable in humans. We hypothesized that one factor contributing to this variability is the presence of specific respiratory tract (RT) microbes. One such microbe is Streptococcus pneumoniae (Sp) that is carried asymptomatically in the RT of many humans. In a mouse co-infection model we found that in contrast to secondary bacterial infection that exacerbates disease, Sp colonization 10 days prior to IAV protects from virus-induced morbidity and lung pathology. Using mutant Sp strains, we identified a critical role for the bacterial virulence factor pneumolysin (PLY) in mediating this protection. Colonization with the PLY-sufficient Sp strain induces expression of the immune-suppressive enzyme arginase 1 in alveolar macrophages (aMø) and correlates with attenuated recruitment and function of pulmonary inflammatory cells. Our study demonstrates a novel role for PLY in Sp-mediated protection by maintaining aMø as "gatekeepers" against virus-induced immunopathology.
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, United States of America.
authors.forename: Amaya I
authors.initials: AI
authors.lastname: Wolf
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, United States of America.
authors.forename: Maura C
authors.initials: MC
authors.lastname: Strauman
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, United States of America.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Mozdzanowska
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, United States of America.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Williams
authors.affiliation: University of Pennsylvania, Philadelphia, PA 19104, United States of America.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Osborne
authors.affiliation: University of Pennsylvania, Philadelphia, PA 19104, United States of America.
authors.forename: Hao
authors.initials: H
authors.lastname: Shen
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, United States of America.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Garlick
authors.affiliation: University of Pennsylvania, Philadelphia, PA 19104, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Artis
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, United States of America.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Hensley
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, United States of America.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Caton
authors.affiliation: University of Pennsylvania, Philadelphia, PA 19104, United States of America.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Weiser
authors.affiliation: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, United States of America. Electronic address: jan@wistar.org.
authors.forename: Jan
authors.initials: J
authors.lastname: Erikson
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D007155:Immunologic Factors / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009975:Orthomyxoviridae / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control; D013296:Streptococcus pneumoniae / Q000201:enzymology*; D013301:Streptolysins / Q000276:immunology* / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D001426:Bacterial Proteins; D007155:Immunologic Factors; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae
keywords: Alveolar macrophages; Arginase I; Immunopathology; Inflammatory monocytes; Influenza virus; Pneumolysin; Protection; Respiratory tract co-infection; Streptococcus pneumoniae; iNOS