Histopathological changes, dynamics of macrophage polarization and deposition of type I and III collagen along the course of experimental hepatic toxocariasis.

Abstract

Toxocariasis is a helminthic infection that predominantly affects the liver and induces significant pathological changes mediated by host immune response. Both M1 and M2 macrophage phenotypes exert opposing yet complementary functions during infection. This study aimed to characterize the sequential immunopathological and fibrogenic events in hepatic toxocariasis over 16 weeks post-infection (wpi) in a murine model. Liver samples were collected from infected mice at different time points, and immunohistochemical (IHC) examination revealed the presence of both macrophage phenotypes up to 8 wpi (group If), indicating mixed immune response. In early stages of infection, macrophage polarization was skewed toward M1 phenotype, with a statistically significant increase in functional M1/M2 macrophage ratio at 2 days post-infection (dpi), followed by a significant decrease in this ratio up to 4 wpi (group Ie) (p&#xa0;<&#xa0;0.001 compared to 2 dpi ). Thereafter, polarization shifted toward M2 phenotype accompanied by a further significant reduction in M1/M2 ratio, whereas at 16 wpi (group Ig), no distinct polarization was observed, although M2 count remained significantly higher than that of the control group (p&#xa0;<&#xa0;0.001). M1 predominance was associated with a higher grades and elevated liver enzyme levels, while M2 cells were associated with significantly lower inflammation grades but higher stages of fibrosis. Type III collagen fibers predominated in early stages of infection, while type I collagen fibers were dominant in the late stages (p&#xa0;<&#xa0;0.001), suggesting a progression toward irreversible fibrotic lesions in chronic hepatic toxocariasis. These findings may support the development of stage-specific diagnostic markers and targeted therapeutic strategies throughout the course of hepatic toxocariasis.