title: Interferon-gamma promotes infection of astrocytes by Trypanosoma cruzi.
abstract: The inflammatory cytokine interferon-gamma (IFNγ) is crucial for immunity against intracellular pathogens such as the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease (CD). IFNγ is a pleiotropic cytokine which regulates activation of immune and non-immune cells; however, the effect of IFNγ 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 IFNγ mRNA. Furthermore, most of the T. cruzi-bearing cells were astrocytes located near IFNγ+ cells. Surprisingly, in vitro experiments revealed that pretreatment with IFNγ 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 IFNγ 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 IFNγ fuels astrocyte infection by T. cruzi and critically implicate IFNγ-stimulated T. cruzi-infected astrocytes as sources of TNF and NO, which may contribute to parasite persistence and CNS pathology in CD.
authors.affiliation: Laboratório de Biologia das Interações, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, Brasil.
authors.forename: Rafael Rodrigues
authors.initials: RR
authors.lastname: Silva
authors.affiliation: Laboratório de Biologia das Interações, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, Brasil.
authors.forename: Rafael M
authors.initials: RM
authors.lastname: Mariante
authors.affiliation: Laboratório Multidisciplinar de Apoio à Pesquisa, Departamento de Medicina Clínica, Universidade Federal Fluminense, Rio de Janeiro, Brasil; Departamento de Patologia, Faculdade de Medicina, Universidade Federal Fluminense, Rio de Janeiro, Brasil.
authors.forename: Andrea Alice
authors.initials: AA
authors.lastname: Silva
authors.affiliation: Laboratório de Biologia das Interações, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, Brasil.
authors.forename: Ana Luiza Barbosa
authors.initials: AL
authors.lastname: dos Santos
authors.affiliation: Laboratório de Biologia das Interações, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, Brasil; Laboratório de Imunologia Celular e Molecular, Centro de Pesquisas René Rachou-Fiocruz, Minas Gerais, Brasil.
authors.forename: Ester
authors.initials: E
authors.lastname: Roffê
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brasil.
authors.forename: Helton
authors.initials: H
authors.lastname: Santiago
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Minas Gerais, Brasil.
authors.forename: Ricardo Tostes
authors.initials: RT
authors.lastname: Gazzinelli
authors.affiliation: Laboratório de Biologia das Interações, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, Brasil.
authors.forename: Joseli
authors.initials: J
authors.lastname: Lannes-Vieira
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000469:parasitology*; D002478:Cells, Cultured; D014355:Chagas Disease / Q000276:immunology / Q000469:parasitology / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D000069285:Infliximab / Q000494:pharmacology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000254:growth & development
chemical_list: D016207:Cytokines; D009569:Nitric Oxide; D007371:Interferon-gamma; D000069285:Infliximab; D019331:NG-Nitroarginine Methyl Ester