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

Edy Y. Kim, John T. Battaile, Anand C. Patel, Yingjian You, Eugene Agapov, Mitchell H. Grayson, Loralyn A. Benoit, Derek E. Byers, Yael Alevy, Jennifer Tucker, Suzanne Swanson, Rose Tidwell, Jeffrey W. Tyner, Jeffrey D. Morton, Mario Castro, Deepika Polineni, G. Alexander Patterson, Reto A. Schwendener, John D. Allard, Gary PeltzMichael J. Holtzman

Research output: Contribution to journalArticle

369 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)633-640
Number of pages8
JournalNature medicine
Volume14
Issue number6
DOIs
StatePublished - Jun 1 2008

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    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. A., Allard, J. D., ... 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. https://doi.org/10.1038/nm1770