Macrophage-mediated Immune Cell Interaction Network and its Synergistic Immune Escape Mechanism in Leishmania Protozoa Infection

Abstract

Leishmania infection is a highly prevalent cause of parasitic disease in tropical and subtropical regions of the world, causing severe clinical symptoms such as skin ulcers and internal organ damage, posing a long-term threat to public health. Macrophages, as the main host cells of Leishmania invasion, have long been a key blind spot in the study of anti-infection immunity because of their dynamic interactions with T cells, dendritic cells (DCs), natural killer cells (NKs) and other immune cells. In this paper, we systematically analyze the synergistic escape mechanism in the macrophage-mediated immune cell network through cytokine inhibition, antigen presentation blockade, and inflammatory modulation. The article demonstrates that infected macrophages inhibit T cell activation, dendritic cell maturation, and NK cell killing through the secretion of TGF-β and IL-10. By down-regulating the expression of MHC molecules, infected macrophages form an "antigen presentation inhibition-immune cell inactivation" cascade. In addition, the study summarizes the reasons why the remodeling of the inflammatory microenvironment promotes parasite survival. This study provides new perspectives for therapeutic strategies targeting immune checkpoints.