IL-4Ralpha-responsive smooth muscle cells contribute to initiation of T(H)2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections.

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

doi:10.1038/mi.2010.46

Article (Scientific journals)

IL-4Ralpha-responsive smooth muscle cells contribute to initiation of T(H)2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections.

Horsnell, W. G.; Vira, A.; Kirstein, F. et al.

2010 • In Mucosal Immunology, 4 (1), p. 83-92

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https://hdl.handle.net/2268/72478

DOI
10.1038/mi.2010.46

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20737001

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Abstract :

[en] Nippostrongylus brasiliensis infections generate pulmonary pathologies that can be associated with strong T(H)2 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-alpha (IL-4Ralpha) responsiveness. At days 7 and 10 post infection (PI), significant airway mucus production was found in IL-4Ralpha(-/lox) control mice, whereas global knockout (IL-4Ralpha(-/-)) and smooth muscle-specific IL-4Ralpha-deficient mice (SM-MHC(Cre) IL-4Ralpha(-/lox)) showed reduced airway mucus responses. Furthermore, interleukin (IL)-13 and IL-5 cytokine production in SM-MHC(Cre) IL-4Ralpha(-/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-4Ralpha and NES-driven responses by smooth muscle cells make important contributions in initiating T(H)2 responses against N. brasiliensis infections.Mucosal Immunology advance online publication 25 August 2010. doi:10.1038/mi.2010.46.

Disciplines :

Immunology & infectious disease

Author, co-author :

Horsnell, W. G.

Vira, A.

Kirstein, F.

Mearns, H.

Hoving, J. C.

Cutler, A. J.

Dewals, Benjamin G ; Université de Liège - ULiège > Immunologie et vaccinologie

Myburgh, E.

Kimberg, M.

Arendse, B.

More authors (4 more)

Language :

English

Title :

IL-4Ralpha-responsive smooth muscle cells contribute to initiation of T(H)2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections.

Publication date :

January 2010

Journal title :

Mucosal Immunology

ISSN :

1933-0219

eISSN :

1935-3456

Publisher :

Nature Publishing Group, United Kingdom

Volume :

Issue :

Pages :

83-92

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 20 September 2010

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