title: 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)-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.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Fnu
authors.initials: F
authors.lastname: Nagajyothi
authors.forename: Mahalia S
authors.initials: MS
authors.lastname: Desruisseaux
authors.forename: Niranjan
authors.initials: N
authors.lastname: Thiruvur
authors.forename: Louis M
authors.initials: LM
authors.lastname: Weiss
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Braunstein
authors.forename: Chris
authors.initials: C
authors.lastname: Albanese
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
authors.forename: Cecilia J
authors.initials: CJ
authors.lastname: de Almeida
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Tanowitz
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000276:immunology / Q000469:parasitology* / Q000648:ultrastructure; D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000276:immunology / Q000469:parasitology* / Q000648:ultrastructure; D000818:Animals; D051242:Caveolin 1 / Q000096:biosynthesis / Q000235:genetics; D014355:Chagas Disease / Q000235:genetics / Q000276:immunology / Q000469:parasitology*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D015151:Immunoblotting; D051379:Mice; D008854:Microscopy, Electron; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051880:Receptors, Notch / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014349:Trypanosoma cruzi / Q000254:growth & development*; D015854:Up-Regulation
chemical_list: D052242:Adiponectin; D051242:Caveolin 1; D016207:Cytokines; D047495:PPAR gamma; D012333:RNA, Messenger; D051880:Receptors, Notch; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases