Inhibition of nitric oxide production of activated mice peritoneal macrophages is independent of the Toxoplasma gondii strain



Título del documento: Inhibition of nitric oxide production of activated mice peritoneal macrophages is independent of the Toxoplasma gondii strain
Revue: Memorias do Instituto Oswaldo Cruz
Base de datos: PERIÓDICA
Número de sistema: 000446502
ISSN: 0074-0276
Autores: 1
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Instituciones: 1Universidade Estadual do Norte Fluminense, Centro de Biociencias e Biotecnologia, Campos dos Goytacazes, Rio de Janeiro. Brasil
2Universidade Federal do Rio de Janeiro, Instituto de Biofisica Carlos Chagas Filho, Rio de Janeiro. Brasil
Año:
Volumen: 116
País: Brasil
Idioma: Inglés
Tipo de documento: Artículo
Enfoque: Experimental, aplicado
Resumen en inglés BACKGROUND Toxoplasma gondii causes toxoplasmosis and is controlled by activated macrophages. However, infection of macrophages by tachyzoites induces TGF-β signaling (TGF-s) inhibiting nitric oxide (NO) production. NO inhibition may be a general escape mechanism of distinct T. gondii strains. OBJECTIVES To evaluate in activated macrophages the capacity of T. gondii strains of different virulence and genetics (RH, type I; ME-49, type II; VEG, type III; P-Br, recombinant) to evade the NO microbicidal defense system and determine LC3 loading to the parasitophorous vacuole. METHODS Activated peritoneal macrophages were infected with the different T. gondii strains, NO-production was evaluated by the Griess reagent, and inducible nitric oxide synthase expression, TGF-s, and LC3 localisation assayed by immunofluorescence. FINDINGS Only RH persisted in macrophages, while VEG was more resistant than P-Br and ME-49. All strains induced TGF-s, degradation of inducible nitric oxide synthase, and NO-production inhibition from 2 to 24 h of infection, but only RH sustained these alterations for 48 h. By 24 h of infection, TGF-s lowered in macrophages infected by ME-49, and P-Br, and NO-production recovered, while VEG sustained TGF-s and NO-production inhibition longer. LC3 loading to parasitophorous vacuole was strain-dependent: higher for ME-49, P-Br and VEG, lower for RH. All strains inhibited NO-production, but only RH sustained this effect probably because it persisted in macrophages due to additional evasive mechanisms as lower LC3 loading to parasitophorous vacuole. MAIN CONCLUSIONS These results support that T. gondii can escape the NO microbicidal defense system at the initial phase of the infection, but only the virulent strain sustain this evasion mechanism
Disciplinas: Medicina
Palabras clave: Microbiología,
Fisiopatología,
Macrófagos,
Activación celular,
Oxido nítrico sintetasa,
Virulencia,
Toxoplasma gondii
Keyword: Microbiology,
Physiopathology,
Macrophages,
Cell activation,
Nitric oxide synthase,
Virulence,
Toxoplasma gondii
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