Article abstract
Nature Medicine 14, 633 - 640 (2008)
Published online: 18 May 2008 | doi:10.1038/nm1770
Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease
Edy Y Kim1, John T Battaile1, Anand C Patel2, Yingjian You1, Eugene Agapov1, Mitchell H Grayson1, Loralyn A Benoit1, Derek E Byers1, Yael Alevy1, Jennifer Tucker1, Suzanne Swanson1, Rose Tidwell1, Jeffrey W Tyner1, Jeffrey D Morton1, Mario Castro1, Deepika Polineni3, G Alexander Patterson3, Reto A Schwendener4, John D Allard5, Gary Peltz5 & Michael J Holtzman1,6
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.
- Department of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
- Department of Pediatrics, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
- Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
- Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, Zurich CH-8057, Switzerland.
- Department of Genetics and Genomics, Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, California 94304, USA.
- Department of Cell Biology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
Correspondence to: Michael J Holtzman1,6 e-mail: holtzmanm@wustl.edu
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