title: Role of tissue protection in lethal respiratory viral-bacterial coinfection.
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.
authors.affiliation: Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. amanda_jamieson@brown.edu
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Jamieson
authors.forename: Lesley
authors.initials: L
authors.lastname: Pasman
authors.forename: Shuang
authors.initials: S
authors.lastname: Yu
authors.forename: Pia
authors.initials: P
authors.lastname: Gamradt
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Homer
authors.forename: Thomas
authors.initials: T
authors.lastname: Decker
authors.forename: Ruslan
authors.initials: R
authors.lastname: Medzhitov
mesh_terms: D000818:Animals; D020170:Caspase 1; D060085:Coinfection / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions / Q000276:immunology; D053583:Interleukin-1beta / Q000378:metabolism; D016952:Legionella pneumophila; D007877:Legionnaires' Disease / Q000276:immunology* / Q000473:pathology; D008168:Lung / Q000382:microbiology / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009975:Orthomyxoviridae; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D020170:Caspase 1