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Role of tissue protection in lethal respiratory viral-bacterial coinfection.

Jamieson AM, Pasman L, Yu S, Gamradt P, Homer RJ, Decker T, Medzhitov R

Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. amanda_jamieson@brown.edu

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.

Published 7 June 2013 in Science, 340(6137): 1230-4.
Full-text of this article is available online (may require subscription).


Articles on Pneumonia published 14 May 2013:

Cytokine markers as predictors of type of respiratory infection in patients during the influenza season.   Am J Emerg Med, 31(5): 816-21.

[Abstract] [Full-text]


Articles on Pneumonia published 10 May 2013:

Effects of phosphoinositide 3-kinase on protease-induced acute and chronic lung inflammation, remodeling, and emphysema in rats.   Chest, 143(4): 1025-35.

[Abstract] [Full-text]

Systemic inflammatory pattern of patients with community-acquired pneumonia with and without COPD.   Chest, 143(4): 1009-17.

[Abstract] [Full-text]


Articles on Pneumonia published 9 May 2013:

Contribution of host, bacterial factors and antibiotic treatment to mortality in adult patients with bacteraemic pneumococcal pneumonia.   Thorax, 68(6): 571-9.

[Abstract] [Full-text]

Impact of the Tohoku earthquake and tsunami on pneumonia hospitalisations and mortality among adults in northern Miyagi, Japan: a multicentre observational study.   Thorax, 68(6): 544-50.

[Abstract] [Full-text]

Number needed to treat in COPD: exacerbations versus pneumonias.   Thorax, 68(6): 540-3.

[Abstract] [Full-text]


Articles on Pneumonia published 7 May 2013:

p53 Integrates host defense and cell fate during bacterial pneumonia.   J Exp Med, 210(5): 891-904.

Cancer and infection are predominant causes of human mortality and derive, respectively, from inadequate genomic and host defenses against environmental agents. The transcription factor p53 plays a central role in human tumor suppression. Despite its expression in immune cells and broad responsiveness to stressors, it is virtually unknown whether p53 regulates host defense against infection. We report that the lungs of naive p53(-/-) mice display genome-wide induction of NF-κB response ... [Abstract] [Full-text]


Articles on Pneumonia published 6 May 2013:

Regulator of calcineurin 1 suppresses inflammation during respiratory tract infections.   J Immunol, 190(10): 5178-86.

Respiratory tract infection with Pseudomonas aeruginosa is a common cause of hospitalization in immune-compromised individuals. However, the molecular mechanisms involved in the immune response to P. aeruginosa lung infection remain incompletely defined. In this study, we demonstrate that the regulator of calcineurin 1 (RCAN1) is a central negative regulator of inflammation in a mouse model of acute bacterial pneumonia using the opportunistic bacterial pathogen P. aeruginosa. RCAN1-deficient ... [Abstract] [Full-text]


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