Regulatory Lymphoid and Myeloid Cells Determine the Cardiac Immunopathogenesis of Trypanosoma cruzi Infection

Abstract

Chagas disease is a multisystemic disorder caused by the protozoan parasite Trypanosoma cruzi, which affects ~8 million people in Latin America, killing 7,000 people annually. Chagas disease is one of the main causes of death in the endemic area and the leading cause of infectious myocarditis in the world. T. cruzi infection induces two phases, acute and chronic, where the infection is initially asymptomatic and the majority of patients will remain clinically indeterminate for life. However, over a period of 10–30 years, ~30% of infected individuals will develop irreversible, potentially fatal cardiac syndromes (chronic chagasic cardiomyopathy [CCC]), and/or dilatation of the gastro-intestinal tract (megacolon or megaesophagus). Myocarditis is the most serious and frequent manifestation of chronic Chagas heart disease and appears in about 30% of infected individuals several years after infection occurs. Myocarditis is characterized by a mononuclear cell infiltrate that includes different types of myeloid and lymphoid cells and it can occur also in the acute phase. T. cruzi infects and replicates in macrophages and cardiomyocytes as well as in other nucleated cells. The pathogenesis of the chronic phase is thought to be dependent on an immune-inflammatory reaction to a low-grade replicative infection. It is known that cytokines produced by type 1 helper CD4+ T cells are able to control infection. However, the role that infiltrating lymphoid and myeloid cells may play in experimental and natural Chagas disease pathogenesis has not been completely elucidated, and several reports indicate that it depends on the mouse genetic background and parasite strain and/or inoculum. Here, we review the role that T cell CD4+ subsets, myeloid subclasses including myeloid-derived suppressor cells may play in the immunopathogenesis of Chagas disease with special focus on myocarditis, by comparing results obtained with different experimental animal models.

Host‐parasite dynamics in Chagas disease from systemic to hyper‐local scales

“…TGF‐β signalling to T cells reduces the risk of late acute mortality, and this appears to involve inhibition of cell proliferation rather than suppression of inflammatory cytokine production 106,163 . Other factors potentially contributing to early inhibition of adaptive immune effector responses include suppressor of cytokine signalling (SOCS), 164 regulatory CD4 + T cells (Tregs) 106,165 and induction of various regulatory/suppressive myeloid cell phenotypes, such as expression of iNOS‐limiting arginase 109,166,167 …”

An Animal Model of Acute and Chronic Chagas Disease With the Reticulotropic Y Strain of Trypanosoma cruzi That Depicts the Multifunctionality and Dysfunctionality of T Cells

“…To date, several animal models have been used to study many aspects of T. cruzi infection (13), including zebrafish (14), rabbits (15), dogs (16), rats (17), mice (18), and non-human primates (19). Given their small size and cost-effectiveness of laboratory maintenance, mice are one of the most promising animal models used to study this parasitic disease (18, 20).…”

Emprego de métodos de imagem de alta-resolução in vivo para estudo das alterações perfusionais e inflamatórias miocárdicas em modelo experimental de cardiomiopatia chagásica crônica no hamster

“…Sugere-se que uma inicial infiltração de macrófagos M1 no coração para controle parasitário, deva ser seguida de proliferação de macrófagos M2 para controlar a inflamação e cicatrizar o coração (SANMARCO et al, 2017;GIRONES, 2018). Entretanto, pacientes chagásicos com formas mais avançadas de cardiopatia apresentam níveis circulantes aumentados de monócitos TNF-α+ e reduzidos de monócitos IL10+ quando comparados a pacientes com formas mais brandas da cardiopatia ou na forma indeterminada da doença (SOUZA et al, 2004;SOUZA et al, 2007;MACHADO et al, 2012).…”

“…Dessa forma, a resposta Th1 parece ser necessária para o controle da infecção no coração, mas se essa resposta não for controlada por células reguladoras, pode levar a uma inflamação excessiva e progressão para CCC (SANOJA et al, 2013;GIRONES, 2018).…”