Immunopathogenesis in Trypanosoma cruzi infection: a role for suppressed macrophages and apoptotic cells

Abstract

During Trypanosoma cruzi infection, macrophages phagocytose parasites and remove apoptotic cells through efferocytosis. While macrophage 1 (M1) produces proinflammatory cytokines and NO and fights infection, M2 macrophages are permissive host cells that express arginase 1 and play a role in tissue repair. The regulation of M1 and M2 phenotypes might either induce or impair macrophage-mediated immunity towards parasite control or persistence in chronic Chagas disease. Here, we highlight a key role of macrophage activation in early immune responses to T. cruzi that prevent escalating parasitemia, heart parasitism, and mortality during acute infection. We will discuss the mechanisms of macrophage activation and deactivation, such as T cell cytokines and efferocytosis, and how to improve macrophage-mediated immunity to prevent parasite persistence, inflammation, and the development of chagasic cardiomyopathy. Potential vaccines or therapy must enhance early T cell-macrophage crosstalk and parasite control to restrain the pathogenic outcomes of parasite-induced inflammation in the heart.

Trypanocidal and Anti-Inflammatory Effects of Three ent-Kaurane Diterpenoids from Gymnocoronis spilanthoides var. subcordata (Asteraceae)

“…Macrophages represent one of the first cellular types that interact with T. c ruzi upon infection. As a phagocyte, it has a dual role: it can contribute to parasite elimination and inflammation in the case of M1 polarized cells or promote tissue repair and fibrosis in the case of M2 macrophages [ 42 ].…”

Small molecule mediators of host-T. cruzi-environment interactions in Chagas disease

“…Antiparasitic responses are fueled by specific metabolic shifts. M1 macrophages are primarily parasiticidal against T. cruzi and are important for acute-stage parasite control (see [102] for more details on the relative roles of M1 and M2 macrophages during T. cruzi infection). M1 macrophage activation with interferon gamma (IFNγAU : Pleasenotethat}IFNg}hasbeenfullyspelledoutas}interferongam ) promotes macrophage glycolysis [103], and increased glycolysis is also observed in monocytes from CD patients [104].…”