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

Front Immunol. 2023 Aug 17:14:1244071. doi: 10.3389/fimmu.2023.1244071. eCollection 2023.

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.

Keywords: Chagas disease; M1 macrophages; T lymphocytes; apoptosis; efferocytosis; fibrosis; heart pathology; inflammation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Chagas Disease*
  • Cytokines
  • Humans
  • Inflammation
  • Macrophages*

Substances

  • Cytokines

Grants and funding

This work was supported by the Brazilian National Research Council (Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq) and the Rio de Janeiro State Science Foundation (Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, FAPERJ). ML is a research fellow at CNPq, Brazil. We also received fellowships from CNPq (TM-S), FAPERJ (NV and TM-S) and the American Association of Immunologists (NV and ML).