PPAR-γ participates in macrophage polarization induced by Pentatrichomonas hominis

Pentatrichomonas hominis ( P. hominis ), a protozoan inhabiting the cecum and colon of humans and vertebrates, is associated with diarrhea. The innate immunity plays a crucial role in defending against parasitic infections. Among these, macrophages are involved in immune evasion, immune surveillance, and tissue repair. Parasites alter the host’s immune homeostasis by modulating macrophage polarization. However, the regulation of macrophage polarization by P. hominis remains unreported. Herein, we found that co-incubation of peritoneal macrophages with P. hominis for 6 h increased CD11c expression, IL-6 and IL-12 levels, and NF-κB p65 phosphorylation. After 24 h of co-culture, CD206 and PPAR-γ expression, as well as IL-4 and IL-10 levels, were elevated in peritoneal macrophages. PPAR-γ agonist GW1929 increased expression of CD206, PPAR-γ, IL-4, and IL-10 in peritoneal macrophages and cecal tissue induced by P. hominis , whereas PPAR-γ antagonist GW9662 had the opposite effect. In mice, GW1929 was validated to alleviate inflammation and injury, whereas GW9662 exacerbated them. Taken together, this study first unveiled that P. hominis modulates macrophage polarization in vitro and that PPAR-γ is associated with this process. GW1929 treatment alleviates inflammation and pathological damage caused by P. hominis infection. These findings provide insights and evidence for further investigation into the innate immune response against P. hominis infection in the host.