Journal Article

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

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

2008

Overview

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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Animals / Antigens, CD - metabolism / Asthma / Biomedical and Life Sciences / Biomedicine / Cancer Research / Care and treatment / Case-Control Studies / CD4-Positive T-Lymphocytes - immunology / Cells, Cultured / Chronic obstructive pulmonary disease / Clinical trials / Disease Models, Animal / Health aspects / Immune response / Immunity, Innate / Immunohistochemistry / Immunology / Infections / Infectious Diseases / Interleukin-13 - biosynthesis / Interleukin-13 - genetics / Killer Cells, Natural - immunology / Killer Cells, Natural - virology / Lung diseases / Macrophages - immunology / Metabolic Diseases / Mice / Mice, Inbred C57BL / Mice, Knockout / Models, Immunological / Molecular Medicine / Mucin 5AC / Mucins - analysis / Mucins - metabolism / Neurosciences / Pathology / Prevention / Pulmonary Disease, Chronic Obstructive - genetics / Pulmonary Disease, Chronic Obstructive - immunology / Pulmonary Disease, Chronic Obstructive - physiopathology / Pulmonary Disease, Chronic Obstructive - virology / Respirovirus Infections - genetics / Respirovirus Infections - immunology / Respirovirus Infections - physiopathology / Respirovirus Infections - virology / Risk factors / RNA, Messenger - analysis / RNA, Messenger - metabolism / Rodents / Sendai virus - physiology / T cells / Time Factors / Trace levels