Recruitment and activation of alternatively activated macrophages by thioredoxin peroxidases in helminth infections

Project Member(s): Donnelly, S.

Funding or Partner Organisation: National Health & Medical Research Council (NHMRC Program Grants)

Start year: 2005

Summary: RNSH/UTS ACEC 0404-027A Alternatively activated macrophages (AAMø) are associated with Th2 inflammatory and noninflammatory processes. The process of macrophage activation to the alternative phenotype is believed to be dependant on the cytokines IL-4 and IL-13. However, the antioxidant, thioredoxin peroxidase (TPx), secreted by the helminth pathogen Fasciola hepatica stimulates macrophages to this alternative activated phenotype in the absence of Th2 cytokines. We hypothesise that TPx participates in the development of Th2 responses in helminth infections via the induction of AAMø that subsequently influence T-cell differentiation. Using both Fasciola hepatica and Schistosoma mansoni as models of helminth infection we will investigate this hypothesis by addressing the following questions: o Are the phenotype of AAMø associated with the Th2 responses driven by Fasciola hepatica and Schistosoma mansoni similar or different? o Do recombinant F. hepatica and S. mansoni TPx recruit and activate AAMø of similar or different phenotype to those observed in infection, and to each other? o Are the recruitment and/or activation of AAMø by TPx independent of Th2 responses? o Do TPx-activated AAMø drive Th2 immune responses by altering T cell differentiation? o What are the extracellular and intracellular mechanisms involved in TPx activation of macrophages?

Publications:

Donnelly, S, Stack, CM, O'Neill, SM, Sayed, AA, Williams, DL & Dalton, JP 2008, 'Helminth 2-Cys peroxiredoxin drives Th2 responses through a mechanism involving alternatively activated macrophages', FASEB JOURNAL, vol. 22, no. 11, pp. 4022-4032.
View/Download from: Publisher's site

FOR Codes: Cellular Immunology