Abstract
Secondary bacterial pneumonia leads to increased morbidity and mortality from influenza virus infections. What causes this increased susceptibility, however, is not well defined. Host defense from infection relies not only on immune resistance mechanisms but also on the ability to tolerate a given level of pathogen burden. Failure of either resistance or tolerance can contribute to disease severity, making it hard to distinguish their relative contribution. We employ a coinfection mouse model of influenza virus and Legionella pneumophila in which we can separate resistance and tolerance. We demonstrate that influenza virus can promote susceptibility to lethal bacterial coinfection, even when bacterial infection is controlled by the immune system. We propose that this failure of host defense is due to impaired ability to tolerate tissue damage.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Caspase 1
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Coinfection / immunology*
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Coinfection / pathology
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Disease Models, Animal
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Host-Pathogen Interactions / immunology
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Interleukin-1beta / metabolism
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Legionella pneumophila*
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Legionnaires' Disease / immunology*
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Legionnaires' Disease / pathology
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Lung / microbiology
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Lung / pathology
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Lung / virology
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Mice
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Mice, Inbred C57BL
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Orthomyxoviridae Infections / immunology*
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Orthomyxoviridae Infections / pathology
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Orthomyxoviridae*
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Pneumonia, Bacterial / immunology*
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Pneumonia, Bacterial / pathology
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Toll-Like Receptor 2 / metabolism
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Toll-Like Receptor 3 / metabolism
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Toll-Like Receptor 4 / metabolism
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Interleukin-1beta
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Tlr2 protein, mouse
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Toll-Like Receptor 2
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Toll-Like Receptor 3
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Toll-Like Receptor 4
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Tumor Necrosis Factor-alpha
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Caspase 1