PloS one, 2015-02, Vol.10 (2), p.e0118600-e0118600
2015
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- Autor(en) / Beteiligte
- Titel
- Interferon-gamma promotes infection of astrocytes by Trypanosoma cruzi
- Ist Teil von
- PloS one, 2015-02, Vol.10 (2), p.e0118600-e0118600
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0118600Titel-ID: cdi_plos_journals_1656299198
- Format
- –
- Schlagworte
- Animals, Astrocytes, Astrocytes - drug effects, Astrocytes - metabolism, Astrocytes - parasitology, Biological response modifiers, Cells, Cultured, Central nervous system, Chagas Disease - immunology, Chagas Disease - parasitology, Chagas Disease - physiopathology, Chagas' disease, Cytokines, Cytokines - metabolism, Female, Gene expression, Health aspects, HIV, Human immunodeficiency virus, Immune system, Immunity, Immunohistochemistry, Infections, Inflammation, Infliximab, Infliximab - pharmacology, Interferon, Interferon-gamma - genetics, Interferon-gamma - metabolism, Interferon-gamma - pharmacology, Intracellular, Laboratory animals, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Monoclonal antibodies, mRNA, NG-Nitroarginine methyl ester, NG-Nitroarginine Methyl Ester - pharmacology, Nitric oxide, Nitric Oxide - metabolism, Oxidative stress, Parasites, Protozoa, RNA, Rodents, Trypanosoma cruzi, Trypanosoma cruzi - growth & development, Tumor necrosis factor-TNF, Tumor necrosis factor-α, Vector-borne diseases, γ-Interferon