Interleukin-4-Promoted T Helper 2 Responses enhance nippostrongylus brasiliensis-induced pulmonary pathology

Mearns, H., Horsnell, W.G.C., Hoving, J.C., Dewals, B., Cutler, A.J., Kirstein, F., Myburgh, E. , Arendse, B. and Brombacher, F. (2008) Interleukin-4-Promoted T Helper 2 Responses enhance nippostrongylus brasiliensis-induced pulmonary pathology. Infection and Immunity, 76(12), pp. 5535-5542. (doi: 10.1128/IAI.00210-08)

Abstract

The role of CD4+ T-cell interleukin-4 (IL-4) receptor alpha (IL-4Rα) expression in T helper 2 (TH2) immune responses has not been defined. To examine this role, we infected CD4+ T-cell IL-4Rα 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-4Rα KO mice, the associated lung pathology was reduced. Infected CD4+ T-cell IL-4Rα KO mice showed abrogation of airway mucus production. Furthermore, CD4+ T-cell IL-4Rα 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-4Rα 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-4Rα KO mice. By day 10 p.i. the TH2 cytokine levels had significantly declined in CD4+ T-cell IL-4Rα 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Myburgh, Dr Elmarie
• Authors: Mearns, H., Horsnell, W.G.C., Hoving, J.C., Dewals, B., Cutler, A.J., Kirstein, F., Myburgh, E., Arendse, B., and Brombacher, F.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Infection and Immunity
• Publisher: American Society for Microbiology
• ISSN: 0019-9567
• ISSN (Online): 1098-5522