IL-4Rα-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections

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.

Item ID: 15241
Item Type: Article (Refereed Research - C1)
ISSN: 1935-3456
Date Deposited: 27 Jan 2011 23:42
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060199 Biochemistry and Cell Biology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
Citation Count from Web of Science Web of Science 6
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