Advances in understanding the role of adipose tissue and mitochondrial oxidative stress in Trypanosoma cruzi infection

Abstract

Trypanosoma cruzi, the etiologic agent of Chagas disease, causes a latent infection that results in cardiomyopathy. Infection with this pathogen is a major socio-economic burden in areas of endemic infection throughout Latin America. The development of chagasic cardiomyopathy is dependent on the persistence of this parasite in host tissues. Pathogenesis of this cardiomyopathy is multifactorial and research indicates that it includes microvascular dysfunction, immune responses to host and parasite antigens, and various vasoactive and lipid mediators produced by both the host and parasite. It has been demonstrated that T. cruzi persists in adipose tissue and uses fat as a nutritional niche in infected hosts. This chronic infection of adipose tissue plays an important role in the pathogenesis and persistence of this infection and involves mitochondrial stress responses as well as the production of various anti-inflammatory adipokines and pro-inflammatory cytokines by both white and brown adipose tissue. The changes in diet in endemic regions of infection have resulted in an epidemic of obesity that has significant implications for the pathogenesis of T. cruzi infection and the development of chagasic cardiomyopathy in infected humans.

Sex Differences in Cardiac Pathology of SARS-CoV2 Infected and Trypanosoma cruzi Co-infected Mice

“…CD has been tightly linked to alterations in metabolic substrate utilization and impairments of mitochondrial oxidative capacity and endoplasmic reticulum functions in the hearts (22,33,(66)(67)(68). It is known that patients with heart disease exhibit a shift from fatty acid oxidation toward greater dependance on glucose as a source for cellular energy adenosine triphosphate (ATP) (69).…”

Brucella abortus Infection Modulates 3T3-L1 Adipocyte Inflammatory Response and Inhibits Adipogenesis

“…The role of adipose tissue in the pathogenesis of infectious diseases has increased attention in recent years (41)(42)(43)(44)(45). Adipose tissue constitutes a nutritionally rich organ for the survival of pathogens such as Mycobacterium tuberculosis, Trypanosoma cruzi, HIV, among others (9,46,47).…”

Prognosis of chronic Chagas heart disease and other pending clinical challenges

“…(13) Growing evidence indicates that parasite persistence is central to the disease by driving the immune response, tissue destruction and chronic inflammation. However, T. cruzi antigens remain scarce and are not always associated with inflammatory foci in the myocardium (14) . The persistence of the parasite in tissues associated with poorly adapted homeostatic mechanisms, such as the oxidative/ antioxidative and proinflammatory/anti-inflammatory processes associated with the dysregulation of the immune response, seems to be essential for the onset and progression of Chagas heart disease.…”

“…(11,12) Recently, studies using hypercaloric diets in animal models have shown an increase in the parasitic load in adipose tissue with a consequent reduction in parasitaemia in cardiac tissue, suggesting that adipose tissue could act as a reservoir for later migration of the parasite to other organs and a possible protective role of adipose tissue in the evolution of chronic Chagas cardiomyopathy. (13,14) The discrepancy between the severity of tissue damage and parasite load has led to the suggestion that the inflammatory immune response of the host is the most important determinant of progression. (13) The balance between immune-mediated parasite containment and damaging inflammation of host tissues likely determines the course of disease.…”