Plasmodium yoelii infection regulates M1 macrophage polarization and function through TLR7/STAT3 signaling pathway

Macrophages play a crucial role in innate immunity and are essential for resisting Plasmodium infection. However, the regulatory mechanisms of Plasmodium infection on macrophage function and subsequent effects on adaptive immune responses remain incompletely understood. In this study, we investigated the functional regulatory mechanism of macrophages during Plasmodium yoelii (P. yoelii) infection and their regulatory role in adaptive immune responses. We found that P. yoelii infection triggered macrophages to polarize towards an M1 phenotype and enhances their phagocytosis. This enhanced function is related to the upregulation of TLR7 expression in macrophages. Notably, the TLR7 agonist R848 alleviated the symptoms of infection in mice, supporting the regulatory role of TLR7. Furthermore, the expression of STAT3 in macrophages also increased upon P. yoelii infection. Inhibitors of STAT3 attenuated the effects induced by TLR7 activation, indicating that the polarization and phagocytosis of macrophages were regulated through a TLR7-STAT3 signaling pathway. We also assessed the role of macrophages in P. yoelii infection by depleting macrophages via Clodronate liposome treatment. The results showed that Clodronate liposome administration increased parasitemia in infected mice and the immune responses of T cells and B cells were also weakened upon macrophage depletion, revealing macrophages are essential for adaptive immunity. In summary, this study demonstrated that Plasmodium infection promoted M1-type polarization and phagocytosis of macrophages through the TLR7-STAT3 signaling pathway, initiating innate and adaptive responses to defend against infection.