Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease. Nat Med 2008 Jun;14(6):633-40
Date
05/20/2008Pubmed ID
18488036Pubmed Central ID
PMC2575848DOI
10.1038/nm1770Scopus ID
2-s2.0-44949257271 (requires institutional sign-in at Scopus site) 445 CitationsAbstract
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.
Author List
Kim EY, Battaile JT, Patel AC, You Y, Agapov E, Grayson MH, Benoit LA, Byers DE, Alevy Y, Tucker J, Swanson S, Tidwell R, Tyner JW, Morton JD, Castro M, Polineni D, Patterson GA, Schwendener RA, Allard JD, Peltz G, Holtzman MJMESH terms used to index this publication - Major topics in bold
AnimalsAntigens, CD
CD4-Positive T-Lymphocytes
Case-Control Studies
Cells, Cultured
Disease Models, Animal
Immunity, Innate
Immunohistochemistry
Interleukin-13
Killer Cells, Natural
Macrophages
Mice
Mice, Inbred C57BL
Mice, Knockout
Models, Immunological
Mucin 5AC
Mucins
Pulmonary Disease, Chronic Obstructive
RNA, Messenger
Respirovirus Infections
Sendai virus
Time Factors