The roles of IL-10 and TGF-beta in controlling IL-4 and IFN-gamma production during experimental Fasciola hepatica infection.
Hosts infected with Fasciola hepatica experience immunosuppression during the acute and chronic phases of the disease. This immunosuppression may allow parasite survival in the face of an ongoing immune response. In bovine hosts early IL-4 and continued IgG1 production is one of the few remaining features of the characteristic type 0/2 helper (Th0/2) response present in the chronic stage of disease. Here we demonstrate elevated levels of parasite-specific, in vitro peripheral blood mononuclear cell (PBMC)-derived transforming growth factor (TGF)-beta1 from the early phases of infection and increasing levels of IL-10 as the infection becomes chronic. In vitro neutralisation of these cytokines during culture of PBMCs from experimentally-infected cattle increased IL-4 and IFN-gamma production in response to parasite-specific and non-specific stimulation. At 4 weeks p.i. neutralisation of TGF-beta results in an increase in parasite driven IL-4, while also having a greater role, compared with IL-10, in influencing specific and non-specific IFN-gamma. At 12 weeks p.i. ex vivo parasite driven IL-4 was not restored by inhibiting either IL-10 or TGF-beta. However IL-10 influenced both parasite-specific and non-specific IFN-gamma production at this time. This highlights the roles of IL-10 and TGF-beta in fasciolosis, however the cellular sources of these have yet to be defined. This suggests that suppression of IFN-gamma production by parasite molecules occurs during infection and it is possible that the suppression of IFN-gamma production may mediate parasite survival in this disease.
Flynn
Robin J
RJ
Veterinary Sciences Centre, School of Agriculture Food Science and Veterinary Medicine, College of Life Sciences, University College Dublin, Ireland. rflynn@mrc-lmb.cam.ac.uk
Mulcahy
Grace
G
D000208:Acute Disease; D000818:Animals; D002417:Cattle; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005210:Fasciola hepatica; D005211:Fascioliasis / Q000276:immunology* / Q000662:veterinary; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology
D016207:Cytokines; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma