Interferon-gamma promotes infection of astrocytes by Trypanosoma cruzi.

ABSTRACT: The inflammatory cytokine interferon-gamma (IFN?) is crucial for immunity against intracellular pathogens such as the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease (CD). IFN? is a pleiotropic cytokine which regulates activation of immune and non-immune cells; however, the effect of IFN? in the central nervous system (CNS) and astrocytes during CD is unknown. Here we show that parasite persists in the CNS of C3H/He mice chronically infected with the Colombian T. cruzi strain despite the increased expression of IFN? mRNA. Furthermore, most of the T. cruzi-bearing cells were astrocytes located near IFN?+ cells. Surprisingly, in vitro experiments revealed that pretreatment with IFN? promoted the infection of astrocytes by T. cruzi increasing uptake and proliferation of intracellular forms, despite inducing increased production of nitric oxide (NO). Importantly, the effect of IFN? on T. cruzi uptake and growth is completely blocked by the anti-tumor necrosis factor (TNF) antibody Infliximab and partially blocked by the inhibitor of nitric oxide synthesis L-NAME. These data support that IFN? fuels astrocyte infection by T. cruzi and critically implicate IFN?-stimulated T. cruzi-infected astrocytes as sources of TNF and NO, which may contribute to parasite persistence and CNS pathology in CD.

SUBMITTER: Silva RR 

PROVIDER: S-EPMC4335051 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature