|
|
||||||||
CUTTING EDGE |
in Host Macrophages1



* Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, Department of Immunology;
University of Texas M. D. Anderson Cancer Center, Houston, TX 77030; and
Department of Infectious Diseases, St. Jude Childrens Research Hospital, Memphis, TN 38105
Infection of mouse macrophages by Toxoplasma gondii renders the cells resistant to proinflammatory effects of LPS triggering. In this study, we show that cell invasion is accompanied by rapid and sustained activation of host STAT3. Activation of STAT3 did not occur with soluble T. gondii extracts or heat-killed tachyzoites, demonstrating a requirement for live parasites. Parasite-induced STAT3 phosphorylation and suppression of LPS-triggered TNF-
and IL-12 was intact in IL-10-deficient macrophages, ruling out a role for this anti-inflammatory cytokine in the suppressive effects of T. gondii. Most importantly, Toxoplasma could not effectively suppress LPS-triggered TNF-
and IL-12 synthesis in STAT3-deficient macrophages. These results demonstrate that T. gondii exploits host STAT3 to prevent LPS-triggered IL-12 and TNF-
production, revealing for the first time a molecular mechanism underlying the parasites suppressive effect on macrophage proinflammatory cytokine production.
This article has been cited by other articles:
![]() |
K. N. Couper, D. G. Blount, and E. M. Riley IL-10: The Master Regulator of Immunity to Infection J. Immunol., May 1, 2008; 180(9): 5771 - 5777. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Nishinakamura, Y. Minoda, K. Saeki, K. Koga, G. Takaesu, M. Onodera, A. Yoshimura, and T. Kobayashi An RNA-binding protein {alpha}CP-1 is involved in the STAT3-mediated suppression of NF-{kappa}B transcriptional activity Int. Immunol., May 1, 2007; 19(5): 609 - 619. [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] |
||||
![]() |
K. C. El Kasmi, J. Holst, M. Coffre, L. Mielke, A. de Pauw, N. Lhocine, A. M. Smith, R. Rutschman, D. Kaushal, Y. Shen, et al. General Nature of the STAT3-Activated Anti-Inflammatory Response J. Immunol., December 1, 2006; 177(11): 7880 - 7888. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. S. Masek, J. Fiore, M. Leitges, S.-F. Yan, B. D. Freedman, and C. A. Hunter Host cell Ca2+ and protein kinase C regulate innate recognition of Toxoplasma gondii J. Cell Sci., November 1, 2006; 119(21): 4565 - 4573. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Kim, B. A. Butcher, C. W. Lee, S. Uematsu, S. Akira, and E. Y. Denkers Toxoplasma gondii Genotype Determines MyD88-Dependent Signaling in Infected Macrophages J. Immunol., August 15, 2006; 177(4): 2584 - 2591. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Bennouna, W. Sukhumavasi, and E. Y. Denkers Toxoplasma gondii Inhibits Toll-Like Receptor 4 Ligand-Induced Mobilization of Intracellular Tumor Necrosis Factor Alpha to the Surface of Mouse Peritoneal Neutrophils Infect. Immun., July 1, 2006; 74(7): 4274 - 4281. [Abstract] [Full Text] [PDF] |
||||
![]() |
Yimin and M. Kohanawa A Regulatory Effect of the Balance between TNF-{alpha} and IL-6 in the Granulomatous and Inflammatory Response to Rhodococcus aurantiacus Infection in Mice J. Immunol., July 1, 2006; 177(1): 642 - 650. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. W. Lee, S. Bennouna, and E. Y. Denkers Screening for Toxoplasma gondii-Regulated Transcriptional Responses in Lipopolysaccharide-Activated Macrophages Infect. Immun., March 1, 2006; 74(3): 1916 - 1923. [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] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |