Trypanosoma cruzi Infection of Cultured Adipocytes Results in an Inflammatory Phenotype

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)-1β, interferon-γ, tumor necrosis factor-α, 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-γ (PPAR-γ). 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.

Altered Regulation of Akt Signaling with Murine Cerebral Malaria, Effects on Long-Term Neuro-Cognitive Function, Restoration with Lithium Treatment

“…We previously demonstrated that ECM results in cognitive impairment associated with white matter damage in mice [43], [45]. The protein tau, a substrate of GSK3β, interacts with microtubules and is associated with early memory loss and cognitive dysfunction in neurodegenerative diseases.…”

Innate immunity and adipose tissue biology

“…Infection with Trypanosoma cruzi, the etiologic agent of Chagas disease, involves adipose tissue. Adipocytes can be infected directly, and expression of IL-1b, IFN-g, TNF-a, CCL2, CCL5, CXC chemokine ligand 10 (CXCL10), TLR2, and TLR9 is increased after infection, whereas expression of adiponectin and PPARg is decreased [60]. Thus, adipose tissue contributes to the inflammatory response observed in Chagas disease.…”

Deficient Adipogenesis of Scleroderma Patient and Healthy African American Monocytes

“…Both caveolin-1 and PPARγ are among the group of proteins in which mutation results in lipodystrophy (Rochford, 2010). Both are downregulated in cultured adipocytes during bacterial infection (Nagajyothi et al, 2008) and in a variety of cell types by TGFβ treatment (Wang et al, 2006; Tourkina et al, 2010; Wei et al, 2010). However, data from our lab and others suggests that TGFβ does not decrease PPARγ levels in monocytes (Figure 4, Kintscher et al, 2002).…”