Current understanding of immunity to Trypanosoma cruzi infection and pathogenesis of Chagas disease

Abstract

Chagas disease caused by Trypanosoma cruzi remains an important neglected tropical disease and a cause of significant morbidity and mortality. No longer confined to endemic areas of Latin America, it is now found in non-endemic areas due to immigration. The parasite may persist in any tissue, but in recent years there has been increased recognition of adipose tissue both as an early target of infection and a reservoir of chronic infection. The major complications of this disease are cardiomyopathy and megasyndromes involving the gastrointestinal tract. The pathogenesis of Chagas disease is complex and multifactorial involving many interactive pathways. The significance of innate immunity, including the contributions of cytokines, chemokines, reactive oxygen species, and oxidative stress, has been emphasized. The role of the components of the eicosanoid pathway such as thromboxane A2 and the lipoxins has been demonstrated to have profound effects as both pro-and anti-inflammatory factors. Additionally, we discuss the vasoconstrictive actions of thromboxane A2 and endothelin-1n Chagas disease. Human immunity to T. cruzi infection and its role in pathogen control and disease progression have not been fully investigated. However, recently, it was demonstrated that a reduction in the anti-inflammatory cytokine IL-10 was associated with clinically significant chronic chagasic cardiomyopathy.

Interferon-γ and other inflammatory mediators in cardiomyocyte signaling during Chagas disease cardiomyopathy

“…These mononuclear cells infiltrating CCC heart tissue express predominantly interferon (IFN)-γ and tumor necrosis factor (TNF)-α, with lower levels of interleukin (IL)-2, IL-4, IL-6 and IL-10. Cytokines like IL-7 and IL-15, which promote T cell survival, are also found to have increased expression in CCC heart tissue [6,7] . Significant IFN-γ signaling was observed in the myocardium of CCC patients, including genes that are not ordinarily expressed by inflammatory cells [8] .…”

Physiology and Pathology of Infectious Diseases: The Autoimmune Hypothesis of Chagas Disease

“…Additional studies have demonstrated that auto-anti-idiotypic antibodies (Ids) from chagasic cardiac disease patients preferentially stimulate B1 cells and CD8 + T cells in magnified proportion as compared to indeterminate patients [29,30]. The lower levels of T cells in the peripheral blood of chagasic cardiac patients suggest that T-cell-mediated immunity should be restricted to inflammatory foci, considering previous reports of the presence of T cells, mainly CD8 + T lymphocytes, in the inflammatory infiltrate of cardiac tissue from individuals infected by T. cruzi [16]. A study using murine experimental model based on infection by T. cruzi demonstrated that the onset of cytokine production by T cells in the cardiac tissue is correlated with the local increase in the expression of cell adhesion molecules that is consistent with the T-lymphocyte migration to the inflammatory milieu [31].…”

“…In fact, the disease outcome toward differential clinical forms is related to many factors including the host-parasite interaction. Several studies have been proposed that the host immunological response plays a major role in the pathogenesis of Chagas disease [16]. Indeed, the T. cruzi can trigger an immune response, since parasite antigen has been consistently found in heart tissue infiltrated from cardiac patients [17,18].…”

“…In this study, the authors propose that chronic inflammation in the cardiac tissue from Chagas disease patients is highly active and is related to a permanent proinflammatory immune pattern that extends from the recent acute phase to the late stages of the chronic phase. Indeed, it is well accepted that the absence of pathology in individuals infected by T. cruzi is associated with the individual's ability to regulate the anti-T. cruzi response, which is responsible for the control of persistent parasitemia and tissue inflammatory damage, characteristic of Chagas disease [16,[32][33][34]. Certainly, the tissue inflammatory damage should be more severe in the absence of regulatory mechanisms involving both innate and adaptive immune responses.…”

Parasite-Derived Neurotrophic Factor/trans-Sialidase of Trypanosoma cruzi Links Neurotrophic Signaling to Cardiac Innate Immune Response

“…hagas' disease, a major cause of morbidity and mortality in Latin America (1)(2)(3), is commonly transmitted by bloodsucking reduviid bugs, which, during a blood meal, release Trypanosoma cruzi. As a metacyclic trypomastigote, T. cruzi gains access to the body through mucosal surfaces or discontinuity in the skin, where it elicits a pronounced inflammatory response.…”