Host immune responses and immune evasion mechanisms in Trypanosoma cruzi: implications for the immunopathogenesis of Chagas disease

Abstract

Chagas disease remains a major neglected tropical disease in Latin America and represents a significant public health challenge in Brazil. The progression of Trypanosoma cruzi infection is highly heterogeneous and reflects a complex interaction between parasite persistence and host immune responses. This narrative review summarizes current knowledge on host immune responses and immune evasion mechanisms during T. cruzi infection and discusses their implications for the immunopathogenesis and clinical progression of Chagas disease. The review included publications indexed in major biomedical databases, prioritizing studies on innate and adaptive immunity, parasite evasion strategies, and associations with chronic disease manifestations. Evidence indicates that innate immune mechanisms involving macrophages, dendritic cells, and natural killer cells are critical for early control of parasitemia through cytokine production, including interferon-gamma and tumor necrosis factor-alpha. Adaptive immunity, particularly CD4⁺ and CD8⁺ T lymphocytes, contributes to parasite control but may also promote chronic inflammation and tissue damage when regulatory mechanisms fail. In parallel, T. cruzi employs multiple immune evasion strategies, including complement inhibition, modulation of antigen-presenting cells, intracellular persistence, and antigenic variability, which facilitate long-term survival in host tissues. These interactions are central to chronic immunopathology, especially Chagas cardiomyopathy. Understanding these processes may contribute to improved diagnostic strategies, support identification of immunological biomarkers associated with disease progression, and inform advances in clinical management and public health approaches.