Virulent Mycobacterium fortuitum restricts NO production by a gamma interferon-activated J774 cell line and phagosome-lysosome fusion

Virulent Mycobacterium fortuitum restricts NO production by a gamma interferon-activated J774 cell line and phagosome-lysosome fusion

Author Silva, Tania Regina Marques da Google Scholar
Freitas, Juliana Ribeiro de Google Scholar
Silva, Queilan Chagas Google Scholar
Figueira, Claudio Pereira Google Scholar
Roxo, Eliana Google Scholar
Leao, Sylvia Cardoso Autor UNIFESP Google Scholar
Freitas, Luiz Antonio Rodrigues de Google Scholar
Veras, Patricia Sampaio Tavares Google Scholar
Institution FIOCRUZ BA R Valdemar Falcao
Universidade Federal da Bahia (UFBA)
Escola Bahiana Med & Saude Publ SSA BA
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract The virulence of different isolates of Mycobacterium has been associated with two morphologically distinguishable colonial variants: opaque (SmOp) and transparent (SmTr). in this report we used an in vitro assay to compare macrophage (Mphi) responses to SmOp and SmTr Mycobacterium fortuitum variants, taking advantage of the fact that these variants were derived from the same isolate. Cells preactivated or not with gamma interferon (IFN-gamma) were infected with SmOp or SmTr M. fortuitum. We showed that SmOp and SmTr induced different levels of nitric oxide (NO) production by IFN-gamma-stimulated Mphi. Indeed, the amount of IFN-gamma-induced NO production by J774 cells was 4.8 to 9.0 times higher by SmOp (23.1 to 37.7 muM) compared to SmTr infection (3.9 to 4.8 muM) (P = 0.0332), indicating that virulent SmTr bacilli restricted NO production. in addition, IFN-gamma-induced NO production by Mphi was higher when correlated with reduction of only avirulent SmOp bacillus viability. SNAP (S-nitroso-N-acetyl-DL-penicillamine)-induced NO production did not modify SmTr viability, indicating its resistance to nitrogen radicals. Electron microscopy studies were performed to evaluate the capacity of phagosomes to fuse with lysosomes labeled with bovine serum albumin-colloidal gold particles. By 24 h postinfection, 69% more phagosome-containing SmOp variant had fused with lysosomes compared to the SmTr-induced phagosomes. in conclusion, these data indicate that virulent SmTr bacilli may escape host defense by restricting IFN-gamma-induced NO production, resisting nitrogen toxic radicals, and limiting phagosome fusion with lysosomes.
Language English
Date 2002-10-01
Published in Infection and Immunity. Washington: Amer Soc Microbiology, v. 70, n. 10, p. 5628-5634, 2002.
ISSN 0019-9567 (Sherpa/Romeo, impact factor)
Publisher Amer Soc Microbiology
Extent 5628-5634
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000178125500035

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