Regulation and function of macrophages in Toxocara canis infection

Macrophages are highly plastic and heterogeneous innate immune cells capable of polarizing into either classically activated or alternatively activated phenotypes, depending on the surrounding microenvironment. This review explores the cross-talk between macrophages and Toxocara canis larvae during infection, emphasizing the role of molecules present in Toxocara excretory-secretory products (TESPs) in regulating macrophage function, polarization and survival, as well as their interactions with macrophage proteins. This narrative review was conducted through a targeted search of peer-reviewed literatures in PubMed, Scopus, and Google Scholar focusing on T. canis, macrophage biology, immune modulation, host-parasite interactions, and the role of macrophages in other nematodes, with studies selected based on relevance to macrophage function, polarization, and associated disease outcomes. During infection, both the parasite and its TESPs drive macrophage activation toward classically activated macrophages (CAMs) and alternatively activated macrophages (AAMs). In the early stage of infection, polarization is predominantly toward CAMs, whereas in later stages macrophages shift toward the AAM phenotype. Macrophages, together with other immune cells, can trap larvae and contribute to granuloma formation. CAMs produce nitric oxide, promote tissue injury and inflammation, and are associated with reduced larval burden. In contrast, AAMs resolve inflammation, facilitate tissue repair, and exert immunoregulatory functions through the production of anti-inflammatory mediators such as IL-10 and TGF-β. Finally, this review discusses the relationship between macrophage responses induced during T. canis infection and the development of associated diseases.