Journal
MUCOSAL IMMUNOLOGY
Volume 4, Issue 1, Pages 83-92Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mi.2010.46
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Funding
- Royal Society (UK)
- National Research Foundation
- Medical Research Council
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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-4R alpha) responsiveness. At days 7 and 10 post infection (PI), significant airway mucus production was found in IL-4R alpha(-/lox) control mice, whereas global knockout (IL-4R alpha(-/-)) and smooth muscle-specific IL-4R alpha-deficient mice (SM-MHCCre IL-4R alpha(-/lox)) showed reduced airway mucus responses. Furthermore, interleukin (IL)-13 and IL-5 cytokine production in SM-MHCCre IL-4R alpha(-/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-4R alpha and NES-driven responses by smooth muscle cells make important contributions in initiating T(H)2 responses against N. brasiliensis infections.
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