ABSTRACT
Widely distributed in the peripheral and lymphoid tissues, macrophages are key effectors of cellular immunity during infection by Trypanosoma cruzi, the etiological agent o f Chagas’ disease. At the onset of infection, insect-transmitted metacyclic trypomastigotes invade tissue-resident macrophages as well as a broad range of nonphagocytic cells. Metacyclic trypomastigotes are able to discriminate host cells through differential engage ment of adhesive glycoproteins that convey either stimulatory or inhibitory signals for cellular invasion. After a few days of intracellular growth, the first cycle of infection terminates with host cell death and consequent release of parasites into interstitial spaces. Trypomastigotes invade and replicate safely in nonprofessional phagocytic cells, taking advantage of the low frequency of MHC-class I restricted CD8 effectors. In the meanwhile, extracellular amastigotes invade tissue-macrophages via the mannose scavenger receptor. As inflammation intensifies, macrophages are innately activated by microbial ligands for Toll-like receptors or by endog enously released danger signals. In spite of innate immunity, the parasites spread to lymphoid tissues, inducing polyclonal lymphocyte activation. Generation of apoptotic lymphocytes in duces TGF-p/PGE2 production by macrophages, which then become permissive to 77 cruzi growth. As the infection continues, tissue parasite load gradually subsides owing to the com bined action of antibodies, type 1 cytokines and effector/memory CD8 T cells. Despite the vigor of anti-parasite immunity, a low-grade and insidious infection is established. Years later, immunoregulatory dysfunctions provoke a progressive form of chronic myocardiopathy in a significant proportion of chagasic patients. In this chapter, we will review information con cerning the role of macrophages as “niches” for intracellular parasite growth during the course of Chagas’ disease.
