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

William Horsnell | Zendy; Alykhan Vira | Zendy; Frank Kirstein | Zendy; Helen Mearns | Zendy; J. Claire Hoving | Zendy; Antony J. Cutler | Zendy; Benjamin G Dewals | Zendy; Elmarie Myburgh | Zendy; Matti Kimberg | Zendy; Berenice Arendse | Zendy; N White | Zendy; Andreas L. Lopata | Zendy; Patricia E. Burger | Zendy; Frank Brombacher | Zendy

Open Access

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

Author(s) -

William Horsnell,

Alykhan Vira,

Frank Kirstein,

Helen Mearns,

J. Claire Hoving,

Antony J. Cutler,

Benjamin G Dewals,

Elmarie Myburgh,

Matti Kimberg,

Berenice Arendse,

N White,

Andreas L. Lopata,

Patricia E. Burger,

Frank Brombacher

Publication year - 2010

Publication title -

mucosal immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 3.596

H-Index - 101

eISSN - 1935-3456

pISSN - 1933-0219

DOI - 10.1038/mi.2010.46

Subject(s) - nippostrongylus brasiliensis , biology , immunology , interleukin 13 , interleukin 4 , mucus , immune system , cytokine , microbiology and biotechnology , ecology

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-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(H)2 responses against N. brasiliensis infections.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research