| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Biochemistry and Immunology, Instituto de Ciências Biológicas, and
School of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil;
Centro de Pesquisas René Rachou, Oswaldo Cruz Foundation, Belo Horizonte, Minas Gerais, Brazil; and
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
Studies performed in vitro suggest that activation of Toll-like receptors (TLRs) by parasite-derived molecules may initiate inflammatory responses and host innate defense mechanisms against Trypanosoma cruzi. Here, we evaluated the impact of TLR2 and myeloid differentiation factor 88 (MyD88) deficiencies in host resistance to infection with T. cruzi. Our results show that macrophages derived from TLR2 -/- and MyD88-/- mice are less responsive to GPI-mucin derived from T. cruzi trypomastigotes and parasites. In contrast, the same cells from TLR2-/- still produce TNF-
, IL-12, and reactive nitrogen intermediates (RNI) upon exposure to live T. cruzi trypomastigotes. Consistently, we show that TLR2-/- mice mount a robust proinflammatory cytokine response as well as RNI production during the acute phase of infection with T. cruzi parasites. Further, deletion of the functional TLR2 gene had no major impact on parasitemia nor on mortality. In contrast, the MyD88-/- mice had a diminished cytokine response and RNI production upon acute infection with T. cruzi. More importantly, we show that MyD88-/- mice are more susceptible to infection with T. cruzi as indicated by the higher parasitemia and accelerated mortality, as compared with the wild-type mice. Together, our results indicate that T. cruzi parasites elicit an alternative inflammatory pathway independent of TLR2. This pathway is partially dependent on MyD88 and necessary for mounting optimal inflammatory and RNI responses that control T. cruzi replication during the early stages of infection.
This article has been cited by other articles:
|
|
 |
|
  V. Schmitz, E. Svensjo, R. R. Serra, M. M. Teixeira, and J. Scharfstein Proteolytic generation of kinins in tissues infected by Trypanosoma cruzi depends on CXC chemokine secretion by macrophages activated via Toll-like 2 receptors J. Leukoc. Biol., June 1, 2009; 85(6): 1005 - 1014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-D. C. Chessler, M. Unnikrishnan, A. K. Bei, J. P. Daily, and B. A. Burleigh Trypanosoma cruzi Triggers an Early Type I IFN Response In Vivo at the Site of Intradermal Infection J. Immunol., February 15, 2009; 182(4): 2288 - 2296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Mesquita, A. B. Carneiro, A. Bafica, F. Gazos-Lopes, C. M. Takiya, T. Souto-Padron, D. P. Vieira, A. Ferreira-Pereira, I. C. Almeida, R. T. Figueiredo, et al. Trypanosoma cruzi Infection Is Enhanced by Vector Saliva through Immunosuppressant Mechanisms Mediated by Lysophosphatidylcholine Infect. Immun., December 1, 2008; 76(12): 5543 - 5552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-D. C. Chessler, L. R. P. Ferreira, T.-H. Chang, K. A. Fitzgerald, and B. A. Burleigh A Novel IFN Regulatory Factor 3-Dependent Pathway Activated by Trypanosomes Triggers IFN-{beta} in Macrophages and Fibroblasts J. Immunol., December 1, 2008; 181(11): 7917 - 7924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Sukhumavasi, C. E. Egan, A. L. Warren, G. A. Taylor, B. A. Fox, D. J. Bzik, and E. Y. Denkers TLR Adaptor MyD88 Is Essential for Pathogen Control during Oral Toxoplasma gondii Infection but Not Adaptive Immunity Induced by a Vaccine Strain of the Parasite J. Immunol., September 1, 2008; 181(5): 3464 - 3473. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Bartholomeu, C. Ropert, M. B. Melo, P. Parroche, C. F. Junqueira, S. M. R. Teixeira, C. Sirois, P. Kasperkovitz, C. F. Knetter, E. Lien, et al. Recruitment and Endo-Lysosomal Activation of TLR9 in Dendritic Cells Infected with Trypanosoma cruzi J. Immunol., July 15, 2008; 181(2): 1333 - 1344. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-M. Chen, P. L. Splinter, S. P. O'Hara, and N. F. LaRusso A Cellular Micro-RNA, let-7i, Regulates Toll-like Receptor 4 Expression and Contributes to Cholangiocyte Immune Responses against Cryptosporidium parvum Infection J. Biol. Chem., September 28, 2007; 282(39): 28929 - 28938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Rodriguez, J. Mages, H. Dietrich, N. Wantia, H. Wagner, R. Lang, and T. Miethke MyD88-dependent changes in the pulmonary transcriptome after infection with Chlamydia pneumoniae Physiol Genomics, July 18, 2007; 30(2): 134 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Debierre-Grockiego, M. A. Campos, N. Azzouz, J. Schmidt, U. Bieker, M. G. Resende, D. S. Mansur, R. Weingart, R. R. Schmidt, D. T. Golenbock, et al. Activation of TLR2 and TLR4 by Glycosylphosphatidylinositols Derived from Toxoplasma gondii J. Immunol., July 15, 2007; 179(2): 1129 - 1137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Koga, S. Hamano, H. Kuwata, K. Atarashi, M. Ogawa, H. Hisaeda, M. Yamamoto, S. Akira, K. Himeno, M. Matsumoto, et al. TLR-Dependent Induction of IFN-beta Mediates Host Defense against Trypanosoma cruzi J. Immunol., November 15, 2006; 177(10): 7059 - 7066. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Monteiro, V. Schmitz, E. Svensjo, R. T. Gazzinelli, I. C. Almeida, A. Todorov, L. B. de Arruda, A. C. T. Torrecilhas, J. B. Pesquero, A. Morrot, et al. Cooperative Activation of TLR2 and Bradykinin B2 Receptor Is Required for Induction of Type 1 Immunity in a Mouse Model of Subcutaneous Infection by Trypanosoma cruzi J. Immunol., November 1, 2006; 177(9): 6325 - 6335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bafica, H. C. Santiago, R. Goldszmid, C. Ropert, R. T. Gazzinelli, and A. Sher Cutting Edge: TLR9 and TLR2 Signaling Together Account for MyD88-Dependent Control of Parasitemia in Trypanosoma cruzi Infection J. Immunol., September 15, 2006; 177(6): 3515 - 3519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Rogers, A. B. Rogers, B. A. Leav, A. Sanchez, E. Vannier, S. Uematsu, S. Akira, D. Golenbock, and H. D. Ward MyD88-Dependent Pathways Mediate Resistance to Cryptosporidium parvum Infection in Mice Infect. Immun., January 1, 2006; 74(1): 549 - 556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. C. Santiago, C. G. Feng, A. Bafica, E. Roffe, R. M. Arantes, A. Cheever, G. Taylor, L. Q. Vierira, J. Aliberti, R. T. Gazzinelli, et al. Mice Deficient in LRG-47 Display Enhanced Susceptibility to Trypanosoma cruzi Infection Associated with Defective Hemopoiesis and Intracellular Control of Parasite Growth J. Immunol., December 15, 2005; 175(12): 8165 - 8172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-M. Chen, S. P. O'Hara, J. B. Nelson, P. L. Splinter, A. J. Small, P. S. Tietz, A. H. Limper, and N. F. LaRusso Multiple TLRs Are Expressed in Human Cholangiocytes and Mediate Host Epithelial Defense Responses to Cryptosporidium parvum via Activation of NF-{kappa}B J. Immunol., December 1, 2005; 175(11): 7447 - 7456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Petersen, K. A. Krumholz, and B. A. Burleigh Toll-Like Receptor 2 Regulates Interleukin-1{beta}-Dependent Cardiomyocyte Hypertrophy Triggered by Trypanosoma cruzi Infect. Immun., October 1, 2005; 73(10): 6974 - 6980. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Drennan, B. Stijlemans, J. Van Den Abbeele, V. J. Quesniaux, M. Barkhuizen, F. Brombacher, P. De Baetselier, B. Ryffel, and S. Magez The Induction of a Type 1 Immune Response following a Trypanosoma brucei Infection Is MyD88 Dependent J. Immunol., August 15, 2005; 175(4): 2501 - 2509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Krishnegowda, A. M. Hajjar, J. Zhu, E. J. Douglass, S. Uematsu, S. Akira, A. S. Woods, and D. C. Gowda Induction of Proinflammatory Responses in Macrophages by the Glycosylphosphatidylinositols of Plasmodium falciparum: CELL SIGNALING RECEPTORS, GLYCOSYLPHOSPHATIDYLINOSITOL (GPI) STRUCTURAL REQUIREMENT, AND REGULATION OF GPI ACTIVITY J. Biol. Chem., March 4, 2005; 280(9): 8606 - 8616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Duthie, M. Kahn, M. White, R. P. Kapur, and S. J. Kahn Both CD1d Antigen Presentation and Interleukin-12 Are Required To Activate Natural Killer T Cells during Trypanosoma cruzi Infection Infect. Immun., March 1, 2005; 73(3): 1890 - 1894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ropert and R. Tostes Gazzinelli Regulatory role of Toll-like receptor 2 during infection with Trypanosoma cruzi Innate Immunity, December 1, 2004; 10(6): 425 - 430. [Abstract] [PDF]
|
|
|
|
|
|
A.-C. Oliveira, J. R. Peixoto, L. B. de Arruda, M. A. Campos, R. T. Gazzinelli, D. T. Golenbock, S. Akira, J. O. Previato, L. Mendonca-Previato, A. Nobrega, et al. Expression of Functional TLR4 Confers Proinflammatory Responsiveness to Trypanosoma cruzi Glycoinositolphospholipids and Higher Resistance to Infection with T. cruzi J. Immunol., November 1, 2004; 173(9): 5688 - 5696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. D. Bolz, R. S. Sundsbak, Y. Ma, S. Akira, C. J. Kirschning, J. F. Zachary, J. H. Weis, and J. J. Weis MyD88 Plays a Unique Role in Host Defense but Not Arthritis Development in Lyme Disease J. Immunol., August 1, 2004; 173(3): 2003 - 2010. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
