| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Institut de Recherche pour le Développement, Montpellier, France;
Center d’Immunologie Pierre-Fabre, Saint-Julien en Genevois, France; and
Hopital Necker, Paris, France
The intracellular protozoan parasite Trypanosoma
cruzi is the etiological agent of Chagas disease. We have
recently identified a T. cruzi-released protein related
to thiol-disulfide oxidoreductase family, called Tc52, which is crucial
for parasite survival and virulence. In vitro, Tc52 in combination with
IFN-
activates human macrophages. In vivo, active immunization with
Tc52 relieves the immunosuppression associated to acute infection and
elicits a specific immune response. As dendritic cells (DC) have a
central role in the initiation of immune responses, we investigated
whether Tc52 may modulate DC activity. We show that Tc52 induces human
DC maturation. Tc52-treated immature DC acquire CD83 and CD86
expression, produce inflammatory chemokines (IL-8, monocyte
chemoattractant protein-1, and macrophage-inflammatory protein-1
),
and present potent costimulatory properties. Tc52 binds to DC by a
mechanism with the characteristics of a saturable receptor system and
signals via Toll-like receptor 2. While Tc52-mediated signaling
involves its reduced glutathione-binding site, another portion of the
molecule is involved in Tc52 binding to DC. Finally, we report that
immunization with Tc52 protects mice in vivo against lethal infection
with T. cruzi. Together these data evidence complex
molecular interactions between the T. cruzi-derived
molecule, Tc52, and DC, and suggest that Tc52 and related class of
proteins might represent a new type of pathogen-associated molecular
patterns. Moreover, the immune protection data suggest that Tc52 is
among candidate molecules that may be used to design an optimal
multicomponent vaccine to control T. cruzi
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]
|
|
|
|
 |
|
 R. Rigano, B. Buttari, E. Profumo, E. Ortona, F. Delunardo, P. Margutti, V. Mattei, A. Teggi, M. Sorice, and A. Siracusano Echinococcus granulosus Antigen B Impairs Human Dendritic Cell Differentiation and Polarizes Immature Dendritic Cell Maturation towards a Th2 Cell Response Infect. Immun., April 1, 2007; 75(4): 1667 - 1678. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Padilla, D. Xu, D. Martin, and R. Tarleton Limited Role for CD4+ T-Cell Help in the Initial Priming of Trypanosoma cruzi-Specific CD8+ T Cells Infect. Immun., January 1, 2007; 75(1): 231 - 235. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
A. F. S. Araujo, B. C. G. de Alencar, J. R. C. Vasconcelos, M. I. Hiyane, C. R. F. Marinho, M. L. O. Penido, S. B. Boscardin, D. F. Hoft, R. T. Gazzinelli, and M. M. Rodrigues CD8+-T-Cell-Dependent Control of Trypanosoma cruzi Infection in a Highly Susceptible Mouse Strain after Immunization with Recombinant Proteins Based on Amastigote Surface Protein 2 Infect. Immun., September 1, 2005; 73(9): 6017 - 6025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Bhatia, M. Sinha, B. Luxon, and N. Garg Utility of the Trypanosoma cruzi Sequence Database for Identification of Potential Vaccine Candidates by In Silico and In Vitro Screening Infect. Immun., November 1, 2004; 72(11): 6245 - 6254. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Antoniazi, H. P. Price, P. Kropf, M. A. Freudenberg, C. Galanos, D. F. Smith, and I. Muller Chemokine Gene Expression in Toll-Like Receptor-Competent and -Deficient Mice Infected with Leishmania major Infect. Immun., September 1, 2004; 72(9): 5168 - 5174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Campos, M. Closel, E. P. Valente, J. E. Cardoso, S. Akira, J. I. Alvarez-Leite, C. Ropert, and R. T. Gazzinelli Impaired Production of Proinflammatory Cytokines and Host Resistance to Acute Infection with Trypanosoma cruzi in Mice Lacking Functional Myeloid Differentiation Factor 88 J. Immunol., February 1, 2004; 172(3): 1711 - 1718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Michailowsky, K. Luhrs, M. O. C. Rocha, D. Fouts, R. T. Gazzinelli, and J. E. Manning Humoral and Cellular Immune Responses to Trypanosoma cruzi-Derived Paraflagellar Rod Proteins in Patients with Chagas' Disease Infect. Immun., June 1, 2003; 71(6): 3165 - 3171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R. P. Ferreira, E. F. Abrantes, C. V. Rodrigues, B. Caetano, G. C. Cerqueira, A. C. Salim, L. F. L. Reis, and R. T. Gazzinelli Identification and characterization of a novel mouse gene encoding a Ras-associated guanine nucleotide exchange factor: expression in macrophages and myocarditis elicited by Trypanosoma cruzi parasites J. Leukoc. Biol., December 1, 2002; 72(6): 1215 - 1227. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
