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

Infect Immun. 2008 Dec;76(12):5535-42. doi: 10.1128/IAI.00210-08. Epub 2008 Sep 22.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Cytokines
  • Interleukin-4