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

Kim, E.Y., et al. Nat. Med. 14, 633-40 (2008).

Speaker: Wei-Cheng Huang (黃偉誠)                 Time: 15:00~16:00, Oct. 8, 2008

Commentator: Dr. Bei-Chang Yang (楊倍昌博士) Place: Room 601

Abstract:

Chronic lung diseases, such as chronic obstructive pulmonary disease and asthma are resulted from aberrant immune responses¹. The establishment of chronic lung diseases is associated with respiratory viral infections², but the pathogenesis remains unclear. In order to investigate the connection between acute viral infection and chronic lung diseases, the authors established a mouse model in which Sendai virus-infected mice developed symptoms of chronic lung diseases, such as mucus production and airway hyperreactivity, while infectious virus was undetectable in the lung. The severity of chronic lung diseases was correlated with the increased Interleukin-13 (IL-13) production predominantly by macrophages in mouse lungs. Although adaptive immune responses are believed to involve in the pathogenesis of chronic lung diseases, however, CD4⁺ and CD8⁺ T cells were not necessary in this model. Moreover, NKT cells accumulated in the lungs were required to regulate macrophage activation and IL-13 production through two pathways. First, NKT cells directly interacted with CD1d molecules on macrophages by semi-invariant T cell receptor. Second, IL-13 secreted by NKT cells bound to the IL-13 receptors on macrophages which showed increased expression of IL-13 receptor alpha chain after viral infection. To examine whether NKT cell-dependent activation of macrophages exhibit in human cases, the authors detected IL-13-producing macrophages and NKT cells in human lung tissues and found that both cell types were increased in the patients with chronic obstructive pulmonary disease. These findings suggests that the immune axis of NKT cell-macrophage-IL-13 may be responsible for the development of chronic lung diseases in humans and provide the evidence that besides adaptive immunity, innate immune responses are also involved in the pathogenesis of chronic lung diseases.

References:

1.         Seino, K. & Taniguchi, M. Functional roles of NKT cell in the immune system. Front. Biosci. 9, 2577-2587 (2004).

2.         Hamelin, M.E., Prince, G.A., Gomez, A.M., Kinkead, R. & Boivin, G. Human metapneumovirus infection induces long-term pulmonary inflammation associated with airway obstruction and hyperresponsiveness in mice. J. Infect. Dis. 193, 1634-1642 (2006).