| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
B and Nitric Oxide1
Institute for the Biotechnology of Infectious Diseases, University of Technology, Sydney, New South Wales, Australia
We propose that the 70-kDa heat shock protein (HSP70) protects
virulent Toxoplasma gondii from the effects of the host
by immunomodulation. This hypothesis was tested using quercetin and
antisense oligonucleotides targeting the start codon of the virulent
T. gondii HSP70 gene. Oligonucleotides were transiently
transfected into two virulent (RH, ENT) and two avirulent (ME49, C)
strains of T. gondii, significantly reducing HSP70
expression in treated parasites. Virulent parasites with reduced HSP70
expression displayed reduced proliferation in vivo, as measured by the
number of tachyzoites present in spleens of infected mice. They also
exhibited an enhanced rate of conversion from tachyzoites to
bradyzoites in vitro. Our results implicate HSP70 as a means by which
virulent strains of T. gondii evade host proinflammatory
responses: when RAW 264.7 cells were exposed to parasites with reduced
HSP70 expression, differential expression of inducible NO synthase
(iNOS) and cell NO production were observed between infections with
normal and HSP70-deficient T. gondii. iNOS message
levels were significantly increased when host cells were infected with
HSP70 reduced virulent tachyzoites and HSP70-related inhibition of iNOS
transcription resulted in altered host NO production by virulent
T. gondii infection. Virulent parasites expressing
reduced levels of HSP70 initiated significantly more NF-
B activation
in host splenocytes than infections with untreated parasites. Neither
proliferative ability nor conversion from tachyzoites to bradyzoites
was affected by lack of HSP70 in avirulent strains of T.
gondii. Furthermore, avirulent T. gondii strains
induced high levels of host iNOS expression and NO production,
regardless of HSP70 expression in these parasites, and inhibition of
HSP70 had no significant effects on translocation of NF-B to the
nucleus. Therefore, the 70-kDa parasite stress protein may be part of
an important survival strategy by which virulent strains down-regulate
host parasiticidal mechanisms.
This article has been cited by other articles:
|
|
 |
|
  H. Fang, F. Aosai, H.-S. Mun, K. Norose, A. K. Ahmed, M. Furuya, and A. Yano Anaphylactic reaction induced by Toxoplasma gondii-derived heat shock protein 70 Int. Immunol., October 1, 2006; 18(10): 1487 - 1497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zimmermann, P. J. Murray, K. Heeg, and A. H. Dalpke Induction of Suppressor of Cytokine Signaling-1 by Toxoplasma gondii Contributes to Immune Evasion in Macrophages by Blocking IFN-{gamma} Signaling J. Immunol., February 1, 2006; 176(3): 1840 - 1847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Cheng, C. Cenciarelli, G. Nelkin, R. Tsan, D. Fan, C. Cheng-Mayer, and I. J. Fidler Molecular Mechanism of hTid-1, the Human Homolog of Drosophila Tumor Suppressor l(2)Tid, in the Regulation of NF-{kappa}B Activity and Suppression of Tumor Growth Mol. Cell. Biol., January 1, 2005; 25(1): 44 - 59. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mamani-Matsuda, J. Rambert, D. Malvy, H. Lejoly-Boisseau, S. Daulouede, D. Thiolat, S. Coves, P. Courtois, P. Vincendeau, and M. D. Mossalayi Quercetin Induces Apoptosis of Trypanosoma brucei gambiense and Decreases the Proinflammatory Response of Human Macrophages Antimicrob. Agents Chemother., March 1, 2004; 48(3): 924 - 929. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Debierre-Grockiego, N. Azzouz, J. Schmidt, J.-F. Dubremetz, H. Geyer, R. Geyer, R. Weingart, R. R. Schmidt, and R. T. Schwarz Roles of Glycosylphosphatidylinositols of Toxoplasma gondii: INDUCTION OF TUMOR NECROSIS FACTOR-{alpha} PRODUCTION IN MACROPHAGES J. Biol. Chem., August 29, 2003; 278(35): 32987 - 32993. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
