Horsnell, W.G.C., Vira, A., Kirstein, F., Mearns, H., Hoving, J.C., Cutler, A.J., Dewals, B., Myburgh, E., Kimberg, M., Arendse, B., White, N., Lopata, A., Burger, P.E., and Brombacher, F. (2011) IL-4Rα-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections. Mucosal Immunology, 4 (1). pp. 83-92.

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Abstract

Nippostrongylus brasiliensis infections generate pulmonary pathologies that can be associated with strong TH2 polarization of the host's immune response. We present data demonstrating N. brasiliensis-driven airway mucus production to be dependent on smooth muscle cell interleukin 4 receptor-α (IL-4Rα) responsiveness. At days 7 and 10 post infection (PI), significant airway mucus production was found in IL-4Rα−/lox control mice, whereas global knockout (IL-4Rα−/−) and smooth muscle-specific IL-4Rα-deficient mice (SM-MHCCre IL-4Rα−/lox) showed reduced airway mucus responses. Furthermore, interleukin (IL)-13 and IL-5 cytokine production in SM-MHCCre IL-4Rα−/lox mice was impaired along with a transient reduction in T-cell numbers in the lung. In vitro treatment of smooth muscle cells with secreted N. brasiliensis excretory–secretory antigen (NES) induced IL-6 production. Decreased protein kinase C (PKC)-dependent smooth muscle cell proliferation associated with cell cycle arrest was found in cells stimulated with NES. Together, these data demonstrate that both IL-4Rα and NES-driven responses by smooth muscle cells make important contributions in initiating TH2 responses against N. brasiliensis infections.

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