Fasciola hepatica infection downregulates Th1 responses in mice

Immune responses induced with helminth parasites have been extensively stud ied, but there is limited information on those to Fasciola hepatica, especi ally on the subtype of T cell induced with this parasite. We investigated t he local and systemic T cell responses of different strains of mice followi ng oral infection with doses of metacercariae from F. hepatica. Spleen cell s from BALB/c and 129Sv/Ev mice given a low-dose (5 metacercariae) infectio n exhibited a Th2 response, producing high levels of the cytokines IL-4 and IL-5, and low levels of IFN-gamma and IL-2. In contrast, C57BL/6 mice show ed a mixed Th1/Th2 response. A more marked polarization to a Th2 response w as observed in BALB/c, 129Sv/Ev exposed to a high-dose (15 metacercariae) i nfection and the C57BL/6 mice also exhibited a clear Th2 response. IL-4 def ective (IL-4(-/-)) C57BL/6 mice infected with 5 metacercariae produced less IFN-gamma and more IL-5 compared to their wild-type C57BL/6 counterparts, suggesting that IL-4 is important in establishing the Th2 type response in murine fasciolosis. However, the secretion of IFN-gamma and IL-2 was comple tely suppressed in the high-dose infection and this was also observed in IL -4(-/-) mice. Thus, liver flukes may secrete molecules that downregulate Th 1 responses. T cell responses in the mesenteric (MLN) and hepatic lymph nod es (HLN) were also examined since newly excysted juveniles infect through t he intestinal wall of their host before migrating to the hepatic tissue. Ce lls from both MLN and HLN secreted higher levels of IL-4 and IL-5 compared to spleen cells. We also observed a difference in cytokine profiles secrete d by the MLN and HLN, which may reflect responses to antigens liberated by newly excysted juveniles and hepatic stage parasites, respectively.