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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.

SUBMITTER: Wolf AI 

PROVIDER: S-EPMC4157663 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Pneumolysin expression by streptococcus pneumoniae protects colonized mice from influenza virus-induced disease.

Wolf Amaya I AI   Strauman Maura C MC   Mozdzanowska Krystyna K   Williams Katie L KL   Osborne Lisa C LC   Shen Hao H   Liu Qin Q   Garlick David D   Artis David D   Hensley Scott E SE   Caton Andrew J AJ   Weiser Jeffrey N JN   Erikson Jan J  

Virology 20140705


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 fr  ...[more]

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