Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity
Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity
Chang YJ, Kim HY, Albacker LA, et al. Nat. immunol. 2011 May 29;12(7):631-8
Speaker: Nai-Chi Yeh (葉乃綺) Time: 14:00~15:00, Sep. 28, 2011
Commentator: Shun-hua Chen, Ph.D (陳舜華教授) Place: Room 601
Abstract
Asthma is a heterogeneous inflammatory disorder of the airways characterized by airway hyper-reactivity (AHR) and chronic airway inflammation. It has been known that allergen-specific T helper 2 (TH2) cells and other cell types which regulate innate immune response are involved in asthma. In this study, the authors want to investigate the mechanisms of AHR induced by influenza virus infection. First, acute AHR response was induced successfully within 5 days in wild type and the recombination-activating gene 2 (Rag2)-deficient mice, lacking both T cell and B cell, infected with influenza virus H3N1. In contrast, ST2-deficient (Il1rl1-/-), Tlr7-/- and MyD88-/- mice were not developed ARH. These results indicated that innate immune response is responsible for the development of H3N1-induced AHR. Further, the large amount of IL-33 was secreted by alveolar macrophages in H3N1-infected mice. This showed IL-33-ST2 signaling pathway was necessary for the AHR response. Moreover, they discovered that innate lymphoid cells, not express Lin but express Sca-1, c-KIT, ST2, CD90.2 (Thy-1.2), CD25 and CD1d markers, presented in the lungs of H3N1-infected mice and produced IL-13 through IL-33 stimulation. Finally, Rag2-/- mice with depletion of innate lymphoid cells and IL-13-/- mice with adoptive transfer of wild type innate lymphoid cells demonstrated innate lymphoid cells were essential for influenza virus-induced AHR. Taken together, this study identifies a new pathway that influenza virus H3N1 infection promotes the development of AHR through IL-33 secretion mainly by alveolar macrophage, binding to ST2 receptor on innate lymphoid cells and stimulation of IL-13 production in the absence of adaptive immune response.
References
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