Author | D'Avila, Heloisa | |
Author | Melo, Rossana C. N. | |
Author | Parreira, Gleydes G. | |
Author | Barroso, Eduardo Werneck | |
Author | Faria Neto, Hugo C. Castro | |
Author | Bozza, Patrícia T. | |
Access date | 2020-01-05T19:56:55Z | |
Available date | 2020-01-05T19:56:55Z | |
Document date | 2006 | |
Citation | D`ÁVILA, Heloisa et al. Mycobacterium bovis Bacillus Calmette-Gue´rin Induces TLR2-Mediated Formation of Lipid Bodies: Intracellular Domains for Eicosanoid Synthesis In Vivo. Journal of Immunology, v. 176, p. 3087-3097, 2006. | pt_BR |
ISSN | 0022-1767 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/38983 | |
Language | eng | pt_BR |
Publisher | American Society of Immunologists | pt_BR |
Rights | restricted access | |
Subject in Portuguese | Mycobacterium bovis Bacillus Calmette-Guérin | pt_BR |
Subject in Portuguese | BCG | pt_BR |
Subject in Portuguese | Corpos lipídicos | pt_BR |
Subject in Portuguese | TLR2 | pt_BR |
Subject in Portuguese | Sinteses de Eicosanóides in vivo | pt_BR |
Title | Mycobacterium bovis bacillus Calmette-Guérin induces TLR2-mediated formation of lipid bodies: intracellular domains for eicosanoid synthesis in vivo | pt_BR |
Type | Article | |
DOI | 10.4049/jimmunol.176.5.3087 | |
Abstract | Differentiation of macrophages into foamy (lipid-laden) macrophages is a common pathological observation in tuberculous granulomas both in experimental settings as well as in clinical conditions; however, the mechanisms that regulate intracellular lipid accumulation in the course of mycobacterial infection and their significance to pathophysiology of tuberculosis are not well understood. In this study, we investigated the mechanisms of formation and function of lipid-laden macrophages in a murine model of tuberculosis. Mycobacterium bovis bacillus Calmette-Guérin (BCG), but not Mycobacterium smegmatis, induced a dose- and time-dependent increase in lipid body-inducible nonmembrane-bound cytoplasmic lipid domain size and numbers. Lipid body formation was drastically inhibited in TLR2-, but not in TLR4-deficient mice, indicating a role for TLR2 in BCG recognition and signaling to form lipid bodies. Increase in lipid bodies during infection correlated with increased generation of PGE2 and localization of cyclooxygenase-2 within lipid bodies. Moreover, we demonstrated by intracellular immunofluorescent localization of newly formed eicosanoid that lipid bodies were the predominant sites of PGE2 synthesis in activated macrophages. Our findings demonstrated that BCG-induced lipid body formation is TLR2 mediated and these structures function as signaling platforms in inflammatory mediator production, because compartmentalization of substrate and key enzymes within lipid bodies has impact on the capacity of activated leukocytes to generate increased amounts of eicosanoids during experimental infection by BCG. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal de Juiz de Fora. Departamento de Biologia. Laboratório de Biologia Celular. Juiz de Fora, MG, Brasil. | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Departamento de Morfologia. Belo Horizonte, MG, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Desenvolvimento de Tecnologia em Saúde. Sefar. Laboratório de Farmacocinética. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | Mycobacterium bovis Bacillus Calmette-Guérin | pt_BR |
Subject | Lipid Bodies | pt_BR |
Subject | TLR2 | pt_BR |
Subject | Eicosanoid synthesis in vivo | pt_BR |
e-ISSN | 1550-6606 | |
Embargo date | 2025-01-01 | |