Interleukin-4-promoted T helper 2 responses enhance Nippostrongylus brasiliensis-induced pulmonary pathology

Helen Mearns, William G C Horsnell, J Claire Hoving, Benjamin Dewals, Antony J Cutler, Frank Kirstein, Elmarie Myburgh, Berenice Arendse, Frank Brombacher

Research output: Contribution to journalArticlepeer-review


The role of CD4(+) T-cell interleukin-4 (IL-4) receptor alpha (IL-4Ralpha) expression in T helper 2 (TH2) immune responses has not been defined. To examine this role, we infected CD4(+) T-cell IL-4Ralpha knockout (KO) mice with the parasitic nematode Nippostrongylus brasiliensis, which induces strong host TH2 responses. Although N. brasiliensis expulsion was not affected in CD4(+) T-cell IL-4Ralpha KO mice, the associated lung pathology was reduced. Infected CD4(+) T-cell IL-4Ralpha KO mice showed abrogation of airway mucus production. Furthermore, CD4(+) T-cell IL-4Ralpha KO mouse lungs contained reduced numbers of lymphocytes and eosinophils. Restimulation of pulmonary region-associated T-cell populations showed that TH2 cytokine responses were disrupted. Secretion of IL-4, but not secretion of IL-13 or IL-5, from mediastinal lymph node CD4(+) T cells was reduced in infected CD4(+) T-cell IL-4Ralpha KO mice. Restimulation of tissue-derived CD4(+) T cells resulted in equivalent levels of IL-4 and IL-13 on day 7 postinfection (p.i.) in control and CD4(+) T-cell IL-4Ralpha KO mice. By day 10 p.i. the TH2 cytokine levels had significantly declined in CD4(+) T-cell IL-4Ralpha KO mice. Restimulation with N. brasiliensis antigen of total lung cell populations and populations with CD4(+) T cells depleted showed that CD4(+) T cells were a key TH2 cytokine source. These data demonstrated that CD4(+) T-cell IL-4 responsiveness facilitates eosinophil and lymphocyte recruitment, lymphocyte localization, and TH2 cytokine production in the allergic pathology associated with N. brasiliensis infections.

Original languageEnglish
Pages (from-to)5535-42
Number of pages8
JournalInfection and Immunity
Issue number12
Publication statusPublished - Dec 2008


  • Animals
  • Chemotaxis, Leukocyte/immunology
  • Cytokines/biosynthesis
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Immunohistochemistry
  • Interleukin-4/deficiency
  • Lung/immunology
  • Mice
  • Mice, Knockout
  • Nippostrongylus/immunology
  • Strongylida Infections/immunology
  • Th2 Cells/immunology

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