Transforming growth factor-β and Th17 responses in resistance to primary murine schistosomiasis mansoni

Discovery of the T-helper (Th) 17 cell lineage and functions in immune responses of mouse and man prompted us to investigate the role of transforming growth factor-beta (TGF-beta) and interleukin (IL)-17 in innate resistance to murine schistosomiasis mansoni. Schistosoma mansoni-infected BALB/c and C57BL/6 mice were administered with recombinant TGF-beta or mouse monoclonal antibody to TGF-beta to evaluate the impact of this cytokine on host immune responses against lung-stage schistosomula, and subsequent effects on adult worm parameters. Developing schistosomula elicited increase in peripheral blood mononuclear cells (PBMC) mRNA expression and/or plasma levels of IL-4, IL-17, and interferon-gamma (IFN-gamma), cytokines known to antagonize each other, resulting in impaired Th1/Th2, and Th17 immune responses and parasite evasion. Mice treated with TGF-beta showed elevated PBMC mRNA expression of IL-6, IL-17, TGF-beta, and TNF-alpha mRNA and increased IL-23 and IL-17 or TGF-beta plasma levels, associated with significantly (P < 0.02-<0.0001) lower S. mansoni adult worm burden compared to controls in both mouse strains, thus suggesting that TGF-beta led to heightened Th17 responses that mediated resistance to the infection. Mice treated with antibody to TGF-beta showed increase in PBMC mRNA expression and plasma levels of IL-4, IL-12p70, and IFN-gamma, and significantly (P < 0.02 and <0.0001) reduced worm burden and liver worm egg counts than untreated mice, indicating that Th1/Th2 immune responses were potentiated, resulting in significant innate resistance to schistosomiasis. The implications of these observations for schistosome immune evasion and vaccination were discussed. (C) 2009 Elsevier Ltd. All rights reserved.