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

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.

Original languageEnglish
Pages (from-to)83-92
Number of pages10
JournalMucosal Immunology
Volume4
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint Dive into the research topics of 'IL-4Rα-responsive smooth muscle cells contribute to initiation of T<sub>H</sub>2 immunity and pulmonary pathology in Nippostrongylus brasiliensis infections'. Together they form a unique fingerprint.

Cite this