The adipocyte as an important target cell for Trypanosoma cruzi infection

被引:158
作者
Combs, TP
Nagajyothi
Mukherjee, NS
de Almeida, CJG
Jelicks, LA
Schubert, W
Lin, Y
Jayabalan, DS
Zhao, DZ
Braunstein, VL
Landskroner-Eiger, S
Cordero, A
Factor, SM
Weiss, LM
Lisanti, MP
Tanowitz, HB
Scherer, PE
机构
[1] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA
[2] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA
[3] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA
[4] Albert Einstein Coll Med, Dept Physiol & Biophys, Bronx, NY 10461 USA
[5] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA
关键词
D O I
10.1074/jbc.M412802200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Adipose tissue plays an active role in normal metabolic homeostasis as well as in the development of human disease. Beyond its obvious role as a depot for triglycerides, adipose tissue controls energy expenditure through secretion of several factors. Little attention has been given to the role of adipocytes in the pathogenesis of Chagas disease and the associated metabolic alterations. Our previous studies have indicated that hyperglycemia significantly increases parasitemia and mortality in mice infected with Trypanosoma cruzi. We determined the consequences of adipocyte infection in vitro and in vivo. Cultured 3T3-L1 adipocytes can be infected with high efficiency. Electron micrographs of infected cells revealed a large number of intracellular parasites that cluster around lipid droplets. Furthermore, infected adipocytes exhibited changes in expression levels of a number of different adipocyte-specific or adipocyte-enriched proteins. The adipocyte is therefore an important target cell during acute Chagas disease. Infection of adipocytes by T. cruzi profoundly influences the pattern of adipokines. During chronic infection, adipocytes may represent an important long-term reservoir for parasites from which relapse of infection can occur. We have demonstrated that acute infection has a unique metabolic profile with a high degree of local inflammation in adipose tissue, hypoadiponectinemia, hypoglycemia, and hypoinsulinemia but with relatively normal glucose disposal during an oral glucose tolerance test.
引用
收藏
页码:24085 / 24094
页数:10
相关论文
共 27 条
[1]   TRYPANOSOMA-BRUCEI - INFECTION IN MURINE DIABETES [J].
AMOLE, BO ;
WITTNER, M ;
HEWLETT, D ;
TANOWITZ, HB .
EXPERIMENTAL PARASITOLOGY, 1985, 60 (03) :342-347
[2]  
BARR SC, 1991, AM J VET RES, V52, P2033
[3]   Detection of live Trypanosoma cruzi in tissues of infected mice by using histochemical stain for β-galactosidase [J].
Buckner, FS ;
Wilson, AJ ;
Van Voorhis, WC .
INFECTION AND IMMUNITY, 1999, 67 (01) :403-409
[4]   Rapid quantitation of Trypanosoma cruzi in host tissue by real-time PCR [J].
Cummings, KL ;
Tarleton, RL .
MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 2003, 129 (01) :53-59
[5]  
dos Santos V M, 1999, Rev Soc Bras Med Trop, V32, P489
[6]   HYPOGLYCEMIA AND HYPERINSULINEMIA IN RODENT MODELS OF SEVERE MALARIA INFECTION [J].
ELASED, K ;
PLAYFAIR, JHL .
INFECTION AND IMMUNITY, 1994, 62 (11) :5157-5160
[7]   Constitutively active mitogen-activated protein kinase kinase 6 (MIKK6) or salicylate induces spontaneous 3T3-L1 adipogenesis [J].
Engelman, JA ;
Berg, AH ;
Lewis, RY ;
Lin, AN ;
Lisanti, MP ;
Scherer, PE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (50) :35630-35638
[8]  
GUARIENTO ME, 1993, BRAZ J MED BIOL RES, V26, P491
[9]   Tumor necrosis factor alpha-mediated toxic shock in Trypanosoma cruzi-infected interleukin 10-deficient mice [J].
Hölscher, C ;
Mohrs, M ;
Dai, WJ ;
Köhler, G ;
Ryffel, B ;
Schaub, GA ;
Mossmann, H ;
Brombacher, F .
INFECTION AND IMMUNITY, 2000, 68 (07) :4075-4083
[10]   Circulating adiponectin levels during human endotoxaemia [J].
Keller, P ;
Moller, K ;
Krabbe, KS ;
Pedersen, BK .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2003, 134 (01) :107-110