Author | Campos, Marco Antônio | |
Author | Almeida, Igor C. | |
Author | Takeuchi, Osamu | |
Author | Akira, Shizuo | |
Author | Valente, Eneida P. | |
Author | Procópio, Daniela O. | |
Author | Travassos, Luiz R. | |
Author | Smith, Jason A. | |
Author | Golenbock, Douglas Taylor | |
Author | Gazzinelli, Ricardo Tostes | |
Access date | 2025-01-17T14:22:38Z | |
Available date | 2025-01-17T14:22:38Z | |
Document date | 2001 | |
Citation | CAMPOS, Marco Antônio et al. Activation of Toll-like receptor-2 by glycosylphosphatidylinositol anchors from a protozoan parasite. J Immunol., v. 167, n. 1, p. 416-3, 2001. | en_US |
ISSN | 0022-1767 | en_US |
URI | https://www.arca.fiocruz.br/handle/icict/68113 | |
Language | eng | en_US |
Publisher | American Association of Immunologists | en_US |
Rights | restricted access | |
Title | Activation of Toll-like receptor-2 by glycosylphosphatidylinositol anchors from a protozoan parasite. | en_US |
Type | Article | |
DOI | 10.4049/jimmunol.167.1.416 | |
Abstract | Glycosylphosphatidylinositol (GPI) anchors and glycoinositolphospholipids (GIPLs) from parasitic protozoa have been shown to exert a wide variety of effects on cells of the host innate immune system. However, the receptor(s) that are triggered by these protozoan glycolipids has not been identified. Here we present evidence that Trypanosoma cruzi-derived GPI anchors and GIPLs trigger CD25 expression on Chinese hamster ovary-K1 cells transfected with CD14 and Toll-like receptor-2 (TLR-2), but not wild-type (TLR-2-deficient) Chinese hamster ovary cells. The protozoan-derived GPI anchors and GIPLs containing alkylacylglycerol and saturated fatty acid chains or ceramide were found to be active in a concentration range of 100 nM to 1 microM. More importantly, the GPI anchors purified from T. cruzi trypomastigotes, which contain a longer glycan core and unsaturated fatty acids in the sn-2 position of the alkylacylglycerolipid component, triggered TLR-2 at subnanomolar concentrations. We performed experiments with macrophages from TLR-2 knockout and TLR-4 knockout mice, and found that TLR-2 expression appears to be essential for induction of IL-12, TNF-alpha, and NO by GPI anchors derived from T. cruzi trypomastigotes. Thus, highly purified GPI anchors from T. cruzi parasites are potent activators of TLR-2 from both mouse and human origin. The activation of TLR-2 may initiate host innate defense mechanisms and inflammatory response during protozoan infection, and may provide new strategies for immune intervention during protozoan infections. | en_US |
Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil. / Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brasil. | en_US |
Affilliation | Universidade de São Paulo. Departamento de Parasitologia. São Paulo, SP, Brasil. | en_US |
Affilliation | Department of Host Defense. Research Institute for Microbial Diseases, Osaka University. Osaka, Japan. | en_US |
Affilliation | Department of Host Defense. Research Institute for Microbial Diseases, Osaka University. Osaka, Japan. | en_US |
Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil. / Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brasil. | en_US |
Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil. / Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brasil. | en_US |
Affilliation | Universidade Federal de São Paulo. Unidade de Oncologia Experimental. São Paulo, SP, Brasil. | en_US |
Affilliation | Boston University School of Medicine. Boston, MA, USA. | en_US |
Affilliation | Boston University School of Medicine. Boston, MA, USA. | en_US |
Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil. / Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brasil. | en_US |
Embargo date | 3100-12-31 | |