The Adipocyte as an Important Target Cell for Trypanosoma cruzi Infection

Philipp E. Scherer,Herbert B. Tanowitz,Vicki L. Braunstein,Shankar Mukherjee,Stephen M. Factor,Aisha Cordero,Linda A. Jelicks,Nagajyothi Nagajyothi,Louis M. Weiss,Terry P. Combs,William Schubert,Shira Landskroner-Eiger,Ying Lin,Michael P. Lisanti,David S. Jayabalan,Cecilia J.G. de Almeida,Dazhi Zhao

doi:10.1074/jbc.m412802200

Philipp E. Scherer, Herbert B. Tanowitz + Show 15 more

Open Access

https://doi.org/10.1074/jbc.m412802200

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Abstract

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.

Highlights

Chagas disease caused by the protozoan parasite Trypanosoma cruzi is endemic in Mexico and Central and South America, where it causes significant morbidity and mortality [1]
Our previous studies have indicated that hyperglycemia significantly increases parasitemia and mortality in mice infected with Trypanosoma cruzi
Infection of Mice with T. cruzi Caused Transient Hypoglycemia during the Acute Phase of the Infection but DidNot Impair Glucose Tolerance—To determine the metabolic consequences of T. cruzi infection, we monitored basal glucose levels as well as insulin sensitivity by means of an oral glucose tolerance test prior to infection, during the acute phase of infection as well as during the chronic stage (ϳ90 days post-infection), and compared it with a cohort of mice that were injected with vehicle only

Summary

Introduction

Chagas disease caused by the protozoan parasite Trypanosoma cruzi is endemic in Mexico and Central and South America, where it causes significant morbidity and mortality [1]. It is a major cause of heart disease in endemic areas. There have been several reports suggesting that diabetes is more common in the setting of increased T. cruzi infection [6, 7]. Our previous studies indicated that when mice with chemically induced diabetes are infected with T. cruzi, they have a higher parasitemia and mortality [9]. The adipose tissue in the acute and chronic state may serve as one of the reservoirs for the parasite from which recrudescence may occur during immune suppression

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