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Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease


Kim, E Y; Battaile, J T; Patel, A C; You, Y; Agapov, E; Grayson, M H; Benoit, L A; Byers, D E; Alevy, Y; Tucker, J; Swanson, S; Tidwell, R; Tyner, J W; Morton, J D; Castro, M; Polineni, D; Patterson, G A; Schwendener, R; Allard, J D; Peltz, G; Holtzman, M J (2008). Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease. Nature Medicine, 14(6):633-640.

Abstract

To understand the pathogenesis of chronic inflammatory disease, we analyzed an experimental mouse model of chronic lung disease with pathology that resembles asthma and chronic obstructive pulmonary disease (COPD) in humans. In this model, chronic lung disease develops after an infection with a common type of respiratory virus is cleared to only trace levels of noninfectious virus. Chronic inflammatory disease is generally thought to depend on an altered adaptive immune response. However, here we find that this type of disease arises independently of an adaptive immune response and is driven instead by interleukin-13 produced by macrophages that have been stimulated by CD1d-dependent T cell receptor-invariant natural killer T (NKT) cells. This innate immune axis is also activated in the lungs of humans with chronic airway disease due to asthma or COPD. These findings provide new insight into the pathogenesis of chronic inflammatory disease with the discovery that the transition from respiratory viral infection into chronic lung disease requires persistent activation of a previously undescribed NKT cell-macrophage innate immune axis.

To understand the pathogenesis of chronic inflammatory disease, we analyzed an experimental mouse model of chronic lung disease with pathology that resembles asthma and chronic obstructive pulmonary disease (COPD) in humans. In this model, chronic lung disease develops after an infection with a common type of respiratory virus is cleared to only trace levels of noninfectious virus. Chronic inflammatory disease is generally thought to depend on an altered adaptive immune response. However, here we find that this type of disease arises independently of an adaptive immune response and is driven instead by interleukin-13 produced by macrophages that have been stimulated by CD1d-dependent T cell receptor-invariant natural killer T (NKT) cells. This innate immune axis is also activated in the lungs of humans with chronic airway disease due to asthma or COPD. These findings provide new insight into the pathogenesis of chronic inflammatory disease with the discovery that the transition from respiratory viral infection into chronic lung disease requires persistent activation of a previously undescribed NKT cell-macrophage innate immune axis.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2008
Deposited On:26 Aug 2008 14:35
Last Modified:05 Apr 2016 12:25
Publisher:Nature Publishing Group
ISSN:1078-8956
Publisher DOI:10.1038/nm1770
PubMed ID:18488036
Permanent URL: http://doi.org/10.5167/uzh-2948

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