Chapter 5 Immune Pathways for Translating Viral Infection into Chronic Airway Disease1

Michael J. Holtzman, Derek E. Byers, Loralyn A. Benoit, John T. Battaile, Yingjian You, Eugene Agapov, Chaeho Park, Mitchell H. Grayson, Edy Y. Kim, Anand C. Patel

Research output: Chapter in Book/Report/Conference proceedingChapter

33 Scopus citations

Abstract

To better understand the immune basis for chronic inflammatory lung disease, we analyzed a mouse model of lung disease that develops after respiratory viral infection. The disease that develops in this model is similar to asthma and chronic obstructive pulmonary disease (COPD) in humans and is manifested after the inciting virus has been cleared to trace levels. The model thereby mimics the relationship of paramyxoviral infection to the development of childhood asthma in humans. When the acute lung disease appears in this model (at 3 weeks after viral inoculation), it depends on an immune axis that is initiated by expression and activation of the high-affinity IgE receptor (FcεRI) on conventional lung dendritic cells (cDCs) to recruit interleukin (IL)-13-producing CD4+ T cells to the lower airways. However, when the chronic lung disease develops fully (at 7 weeks after inoculation), it is driven instead by an innate immune axis that relies on invariant natural killer T (iNKT) cells that are programmed to activate macrophages to produce IL-13. The interaction between iNKT cells and macrophages depends on contact between the semi-invariant Vα14Jα18-TCR on lung iNKT cells and the oligomorphic MHC-like protein CD1d on macrophages as well as NKT cell production of IL-13 that binds to the IL-13 receptor (IL-13R) on the macrophage. This innate immune axis is also activated in the lungs of humans with severe asthma or COPD based on detection of increased numbers of iNKT cells and alternatively activated IL-13-producing macrophages in the lung. Together, the findings identify an adaptive immune response that mediates acute disease and an innate immune response that drives chronic inflammatory lung disease in experimental and clinical settings.

Original languageEnglish
Title of host publicationAdvances in Immunology
EditorsFrederick Alt
Pages245-276
Number of pages32
DOIs
StatePublished - Jun 2 2009

Publication series

NameAdvances in Immunology
Volume102
ISSN (Print)0065-2776
ISSN (Electronic)1557-8445

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    Holtzman, M. J., Byers, D. E., Benoit, L. A., Battaile, J. T., You, Y., Agapov, E., Park, C., Grayson, M. H., Kim, E. Y., & Patel, A. C. (2009). Chapter 5 Immune Pathways for Translating Viral Infection into Chronic Airway Disease1. In F. Alt (Ed.), Advances in Immunology (pp. 245-276). (Advances in Immunology; Vol. 102). https://doi.org/10.1016/S0065-2776(09)01205-X