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

W. G.C. Horsnell; A. Vira; F. Kirstein; H. Mearns; J. C. Hoving; A. J. Cutler; B. Dewals; E. Myburgh; M. Kimberg; B. Arendse; N. White; A. Lopata; P. E. Burger; F. Brombacher

doi:10.1038/mi.2010.46

IL-4Rα-responsive smooth muscle cells contribute to initiation of T_H2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections

W. G.C. Horsnell, A. Vira, F. Kirstein, H. Mearns, J. C. Hoving, A. J. Cutler, B. Dewals, E. Myburgh, M. Kimberg, B. Arendse, N. White, A. Lopata, P. E. Burger, F. Brombacher

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27 Scopus citations

Abstract

Nippostrongylus brasiliensis infections generate pulmonary pathologies that can be associated with strong T_H2 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-MHC Cre IL-4Rα /lox) showed reduced airway mucus responses. Furthermore, interleukin (IL)-13 and IL-5 cytokine production in SM-MHC Cre 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 T_H2 responses against N. brasiliensis infections.

Original language	English
Pages (from-to)	83-92
Number of pages	10
Journal	Mucosal Immunology
Volume	4
Issue number	1
DOIs	https://doi.org/10.1038/mi.2010.46
State	Published - Jan 2011

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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., & Brombacher, F. (2011). IL-4Rα-responsive smooth muscle cells contribute to initiation of T_H2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections. Mucosal Immunology, 4(1), 83-92. https://doi.org/10.1038/mi.2010.46

@article{3f7f58678bc544e2b3233ecb25efc227,

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

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-MHC Cre IL-4Rα /lox) showed reduced airway mucus responses. Furthermore, interleukin (IL)-13 and IL-5 cytokine production in SM-MHC Cre 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.",

author = "Horsnell, {W. G.C.} and A. Vira and F. Kirstein and H. Mearns and Hoving, {J. C.} and Cutler, {A. J.} and B. Dewals and E. Myburgh and M. Kimberg and B. Arendse and N. White and A. Lopata and Burger, {P. E.} and F. Brombacher",

note = "Funding Information: We thank Lizette Fick, Wendy Green, Zanaria Abbas, and Reagon Peterson for their technical assistance and Natalie Nieuwenhuizen and Saeeda Bobat for critical reading of the manuscript. The project was funded by the Royal Society (UK), National Research Foundation (SA), and Medical Research Council (SA). B. Dewals is a postdoctoral researcher of the Fonds National de la Recherche Scientifique (FNRS), Belgium.",

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doi = "10.1038/mi.2010.46",

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Horsnell, WGC, Vira, A, Kirstein, F, Mearns, H, Hoving, JC, Cutler, AJ, Dewals, B, Myburgh, E, Kimberg, M, Arendse, B, White, N, Lopata, A, Burger, PE & Brombacher, F 2011, 'IL-4Rα-responsive smooth muscle cells contribute to initiation of T_H2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections', Mucosal Immunology, vol. 4, no. 1, pp. 83-92. https://doi.org/10.1038/mi.2010.46

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T1 - IL-4Rα-responsive smooth muscle cells contribute to initiation of TH2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections

AU - Horsnell, W. G.C.

AU - Vira, A.

AU - Kirstein, F.

AU - Mearns, H.

AU - Hoving, J. C.

AU - Cutler, A. J.

AU - Dewals, B.

AU - Myburgh, E.

AU - Kimberg, M.

AU - Arendse, B.

AU - White, N.

AU - Lopata, A.

AU - Burger, P. E.

AU - Brombacher, F.

N1 - Funding Information: We thank Lizette Fick, Wendy Green, Zanaria Abbas, and Reagon Peterson for their technical assistance and Natalie Nieuwenhuizen and Saeeda Bobat for critical reading of the manuscript. The project was funded by the Royal Society (UK), National Research Foundation (SA), and Medical Research Council (SA). B. Dewals is a postdoctoral researcher of the Fonds National de la Recherche Scientifique (FNRS), Belgium.

PY - 2011/1

Y1 - 2011/1

N2 - 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-MHC Cre IL-4Rα /lox) showed reduced airway mucus responses. Furthermore, interleukin (IL)-13 and IL-5 cytokine production in SM-MHC Cre 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.

AB - 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-MHC Cre IL-4Rα /lox) showed reduced airway mucus responses. Furthermore, interleukin (IL)-13 and IL-5 cytokine production in SM-MHC Cre 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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IL-4Rα-responsive smooth muscle cells contribute to initiation of T_H2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections

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