Transforming growth factor-beta 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.
Tallima
Hatem
H
Zoology Department, Faculty of Science, Cairo University, Cairo 12613, Egypt.
Salah
Mohamed
M
Guirguis
Fatem R
FR
El Ridi
Rashika
R
D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D019070:Cell Lineage; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D012555:Schistosomiasis mansoni / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000909:Antibodies, Helminth; D020381:Interleukin-17; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta