The cytokine responses to helminth parasitic infections are well established in both laboratory models and human infections; down-regulation of Th1 response and up-regulation of Th2 responses are hallmarks of successful infection.33-35 Here, we demonstrate that Th1-inducing selleck cytokine responses are immunoprotective for the host
and prevent a successful infection. We investigated systemic levels of cytokine expression in the uninfected and infected Mta1+/+ and age-matched Mta1−/− mice. We also measured levels of IgG in control and infected mice against a crude antigen extract of adult O. viverrini. Antibody responses to O. viverrini were similar in both genotypes, indicating that Mta1+/+ and age-matched Mta1−/− mice were similarly infected by metacercariae at the onset of the experiment (Fig. 3A,B). Among the Th1 cytokines examined, elevated levels of interleukin-12 (IL-12) and IFN-γ were observed in Mta1−/− mice compared with infected wild-type mice (Fig. 4A,B). The levels of other Th1 cytokines studied remained similar between both genotypes. Comparative analysis XL184 supplier of systemic levels of other cytokines in response to O. viverrini revealed curious profiles. Mta1−/− mice expressed higher
levels of the immunomodulator, IL-10 (Fig. 4E). Of the other cytokines assayed, there was a significant increase in proinflammatory cytokine IL-6 in Mta1+/+ compared with Mta1−/− mice (Fig. 4F). Parasite-induced IL-6 expression has been reported to be critical for advanced periductal fibrosis during chronic opisthorchiasis and hepatic abnormalities.18 Levels of TNF-α remained unaffected between both genotypes (Fig. 4D). Together, these results suggest that MTA1 is a host determinant for optimum cytokine response and immune evasion after O. viverrini infection. The immune response during opisthorchiasis remains, in general, poorly understood. We next evaluated whether
systemic changes in cytokine profiles observed between the Mta1+/+ and Mta1−/− mice was also observed in O. viverrini target tissues such as the liver. We used selleckchem quantitative RT-PCR to ascertain local levels of cytokines using RNA isolated from infected Mta1+/+ and Mta1−/− mice. The Th1 cytokine IL-12 was significantly up-regulated in Mta1−/− mice compared with age-matched Mta1+/+ mice. Levels of immunomodulatory IL-10 and the proinflammatory cytokines paralleled the systemic expression profile observed between both genotypes (Fig. 5A-D). Because Mta1+/+ mice exhibited cytokine profiles that we hypothesize favor parasite infection, we next evaluated whether MTA1 mRNA levels were modulated after O. viverrini infection. We found that there was a robust increase in MTA1 mRNA levels in livers of Mta1+/+ mice after infection (Fig. 5E), indicating that infectious agents such as parasitic helminths (including O. viverrini) use common host-regulatory factors for successful infection and modulation of the host response for immune evasion. Infection with O.