Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/7103
Title: Cutting edge: TLR9 and TLR2 signaling together account for MyD88-dependent control of parasitemia in Trypanosoma cruzi infection
Authors: Bafica, Andre Luiz Barbosa
Santiago, Helton da Costa
Goldszmid, Romina
Ropert, Catherine
Gazzinelli, Ricardo Tostes
Sher, Alan
Affilliation: National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, USA
Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Bioquımica e Imunologia. Belo Horizonte, MG, Brazil
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, USA
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratorio de Imunopatologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Bioquımica e Imunologia. Belo Horizonte, MG, Brazil/Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratorio de Imunopatologia. Belo Horizonte, MG, Brazil
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Immunobiology Section. Bethesda, USA
Abstract: Activation of innate immune cells by Trypanosoma cruzi-derived molecules such as GPI anchors and DNA induces proinflammatory cytokine production and host defense mechanisms. In this study, we demonstrate that DNA from T. cruzi stimulates cytokine production by APCs in a TLR9-dependent manner and synergizes with parasite-derived GPI anchor, a TLR2 agonist, in the induction of cytokines by macrophages. Compared with wild-type animals, T. cruzi-infected Tlr9(-/-) mice displayed elevated parasitemia and decreased survival. Strikingly, infected Tlr2(-/-)Tlr9(-/-) mice developed a parasitemia equivalent to animals lacking MyD88, an essential signaling molecule for most TLR, but did not show the acute mortality displayed by MyD88(-/-) animals. The enhanced susceptibility of Tlr9(-/-) and Tlr2(-/-)Tlr9(-/-) mice was associated with decreased in vivo IL-12/IFN-gamma responses. Our results reveal that TLR2 and TLR9 cooperate in the control of parasite replication and that TLR9 has a primary role in the MyD88-dependent induction of IL-12/IFN-gamma synthesis during infection with T. cruzi.
Keywords: Adaptor proteins
Signal Transducing/physiology
Antigen-Presenting Cells/immunology
Chagas Disease/immunology
Interferon-gamma/metabolism
Toll-Like Receptor 2/genetics
Issue Date: 2006
Publisher: American Association of Immunologists
Citation: BAFICA, Andre et al. Cutting edge: TLR9 and TLR2 signaling together account for MyD88-dependent control of parasitemia in Trypanosoma cruzi infection. J Immunol. 2006 Sep 15;177(6):3515-9.
ISSN: 0022-1767
Copyright: restricted access
Appears in Collections:MG - IRR - Artigos de Periódicos

Files in This Item:
File Description SizeFormat 
9.pdf407.61 kBAdobe PDFThumbnail
    Request a copy


FacebookTwitterDeliciousLinkedInGoogle BookmarksBibTex Format mendeley Endnote DiggMySpace

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.