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, Frank Brombacher

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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-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.

Original languageEnglish
Pages (from-to)83-92
Number of pages10
JournalMucosal Immunology
Issue number1
Publication statusPublished - Jan 2011


  • Animals
  • Cell Cycle/genetics
  • Flow Cytometry
  • Interleukin-13/biosynthesis
  • Interleukin-4 Receptor alpha Subunit/genetics
  • Interleukin-5/biosynthesis
  • Interleukin-6/biosynthesis
  • Lung Diseases, Parasitic/immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mucus/metabolism
  • Myocytes, Smooth Muscle/immunology
  • Nippostrongylus/immunology
  • Protein Kinase C/metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Strongylida Infections/immunology
  • Th2 Cells/immunology

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