By the same authors

From the same journal

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

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Published copy (DOI)

Author(s)

  • 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

Department/unit(s)

Publication details

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

Abstract

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.

    Research areas

  • 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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