Trypanosoma cruzi infection of cultured adipocytes results in an inflammatory phenotype.

Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
Obesity (Impact Factor: 4.39). 10/2008; 16(9):1992-7. DOI: 10.1038/oby.2008.331
Source: PubMed

ABSTRACT Infection with Trypanosoma cruzi, the etiologic agent of Chagas disease is accompanied by an intense inflammatory reaction. Our laboratory group has identified adipose tissue as one of the major sites of inflammation during disease progression. Because adipose tissue is composed of many cell types, we were interested in investigating whether the adipocyte per se was a source of inflammatory mediators in this infection. Cultured adipocytes were infected with the Tulahuen strain of T. cruzi for 48-96 h. Immunoblot and quantitative PCR (qPCR) analyses demonstrated an increase in the expression of proinflammatory cytokines and chemokines, including interleukin (IL)-1 beta, interferon-gamma, tumor necrosis factor-alpha, CCL2, CCL5, and CXCL10 as well as an increase in the expression of Toll-like receptors-2 and 9 and activation of the notch pathway. Interestingly, caveolin-1 expression was reduced while cyclin D1 and extracellular signal-regulated kinase (ERK) expression was increased. The expression of PI3kinase and the activation of AKT (phosphorylated AKT) were increased suggesting that infection may induce components of the insulin/IGF-1 receptor cascade. There was an infection-associated decrease in adiponectin and peroxisome proliferator-activated receptor-gamma (PPAR-gamma). These data provide a mechanism for the increase in the inflammatory phenotype that occurs in T. cruzi-infected adipocytes. Overall, these data implicate the adipocyte as an important target of T. cruzi, and one which contributes significantly to the inflammatory response observed in Chagas disease.

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    • "The presence of parasites within chronically infected fat pads may lead to insulin resistance, causing increased lipolysis with chronically elevated local free fatty acid levels that in turn trigger an increased infiltration of macrophages. As adipose tissue is composed of many cell types, direct evidence of the consequences of infection on cultured adipocytes provides important support for an inflammatory phenotype (Nagajyothi et al., 2008). T. cruzi infection of cultured adipocytes results in increased expression of PI3 kinase and the activation of protein kinase B (AKT), strongly suggesting the induction of the insulin/IGF-1 receptor pathway. "
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    • "The mRNA levels of macrophage-specific F4/80 gene and TLR-9 were measured using the published primers and protocol. The measurements were normalized to the mRNA levels of HPRT gene as described earlier (Nagajyothi et al. 2008). "
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    • "Additionally, infection was accompanied by an upregulation of inflammatory mediators including, cytokines and chemokines which began early in infection and persisted [10]. Since adipose tissue is a heterogeneous tissue composed of many cell types we also infected cultured adipocytes derived from fibroblasts and found that there was an upregulation of many inflammatory mediators [18]. In the current report we demonstrate that primary adipocytes can be infected with trypomastigotes of T. cruzi. "
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