Evidence for Trypanosoma cruzi in adipose tissue in human chronic Chagas disease.

Department of Basic Nursing, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil.
Microbes and Infection (Impact Factor: 2.92). 06/2011; 13(12-13):1002-5. DOI: 10.1016/j.micinf.2011.06.002
Source: PubMed

ABSTRACT Trypanosoma cruzi the cause of Chagas disease persists in tissues of infected experimental animals and humans. Here we demonstrate the persistence of the parasite in adipose tissue from of three of 10 elderly seropositive patients with chronic chagasic heart disease. Nine control patients had no parasites in the fat. We also demonstrate that T. cruzi parasitizes primary adipocytes in vitro. Thus, in humans as in mice the parasite may persist in adipose tissue for decades and become a reservoir of infection.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Chagasic cardiomyopathy caused by Trypanosoma cruzi is a major health concern in Latin America and among immigrant populations in non-endemic areas. T. cruzi has a high affinity for host lipoproteins and uses the low density lipoprotein receptor (LDLr) for invasion. Herein, we report that T. cruzi infection is associated with an accumulation of LDL and cholesterol in tissues in both acute and chronic murine Chagas disease. Similar findings were observed in tissue samples from a human case of Chagasic cardiomyopathy. T. cruzi infection of cultured cells displayed increased invasion with increasing cholesterol levels in the medium. Studies of infected host cells demonstrated alterations in their cholesterol regulation. T. cruzi invasion/infection via LDLr appears to be involved in changes in intracellular cholesterol homeostasis. The observed changes in intracellular lipids and associated oxidative stress due to these elevated lipids may contribute to the development of Chagasic cardiomyopathy.
    Microbes and Infection 01/2014; · 2.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic Trypanosoma cruzi infections lead to cardiomyopathy in 20-30% of cases. A causal link between cardiac infection and pathology has been difficult to establish because of a lack of robust methods to detect scarce, focally distributed parasites within tissues. We developed a highly sensitive bioluminescence imaging system based on T. cruzi expressing a novel luciferase that emits tissue-penetrating orange-red light. This enabled long-term serial evaluation of parasite burdens in individual mice with an in vivo limit of detection of significantly less than 1000 parasites. Parasite distributions during chronic infections were highly focal and spatiotemporally dynamic, but did not localize to the heart. End-point ex vivo bioluminescence imaging allowed tissue-specific quantification of parasite loads with minimal sampling bias. During chronic infections, the gastro-intestinal tract, specifically the colon and stomach, was the only site where T. cruzi infection was consistently observed. Quantitative PCR-inferred parasite loads correlated with ex vivo bioluminescence and confirmed the gut as the parasite reservoir. Chronically infected mice developed myocarditis and cardiac fibrosis, despite the absence of locally-persistent parasites. These data identify the gut as a permissive niche for long-term T. cruzi infection and show that canonical features of Chagas disease can occur without continual myocardium-specific infection.
    Cellular Microbiology 04/2014; · 4.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Trypanosoma cruzi is the etiologic agent of Chagas disease. Approximately 10 million people are infected worldwide. We have previously reported that in individuals infected with T. cruzi, apolipoprotein A-I (Apo A-I), the major structural component of host high-density lipoprotein, was truncated into fragments that are specific to Chagas disease and have the potential to be used as diagnostic biomarkers. We investigated the possibility that cruzipain, the major cysteine protease of T. cruzi, is responsible for truncating host Apo A-I. We found that due to Apo A-I truncation, the high-density lipoprotein subspecies profile is altered in individuals with Chagas disease compared with healthy controls. Western blot analysis revealed that both purified Apo A-I protein and Apo A-I in the high-density lipoprotein complex were susceptible to cruzipain cleavage, and the sizes of the truncation product in the latter matched the sizes of Apo A-I biomarkers. We also found that in vitro feeding T. cruzi-infected differentiated human adipocytes with purified human high-density lipoprotein led to the appearance of the biomarker fragments of Apo A-I. Cruzipain is found both on the cytoplasmic membrane and in the internal lysosomal structure of T. cruzi. We demonstrate that cruzipain from both sources contributes to the production of Apo A-I truncation in the biomarker set.
    American Journal Of Pathology 02/2014; · 4.52 Impact Factor


Available from
Jun 5, 2014