Acute to chronic liver macrophage response in Syrian hamsters infected with the liver fluke Opisthorchis felineus.

Abstract

Opisthorchis felineus infection is endemic to Russia and Eastern European countries. Although hepatobiliary pathology associated with O. felineus liver fluke infection is well characterized, the hepatic immune response, particularly during the transition from acute to chronic infection, remains insufficiently studied. Here, we investigated macrophage polarization in the liver of Mesocricetus auratus over 1-52 weeks post infection with O. felineus. Histological examination revealed progressive periductal fibrosis and bile duct proliferation, accompanied by cholangiofibrosis. The inflammatory response peaked at week 3 post infection. A mixed M1/M2 macrophage polarization profile emerged during acute infection. We further assessed the effects of O. felineus excretory-secretory product on macrophages differentiated from primary human blood monocytes in vitro. Treatment with excretory-secretory product suppressed pro-inflammatory markers (IL1B, TNFA) in unpolarized, M1-, and M2-like macrophages, accompanied with suppression of TGFB1 in M2-like macrophages, indicative of a mixed immunomodulatory effect. Serum cytokine profiling by ELISA corroborated these findings, revealing elevated IL-6 and TNF-α levels during acute infection (peaking at week 3), followed by alleviation of inflammation during chronic infection. Collectively, these data highlight the capacity of O. felineus excretory-secretory product to modulate macrophage polarization and to promote reparative remodeling in host liver tissue.