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Infection and Immunity, July 2006, p. 4274-4281, Vol. 74, No. 7
0019-9567/06/$08.00+0     doi:10.1128/IAI.01573-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Toxoplasma gondii Inhibits Toll-Like Receptor 4 Ligand-Induced Mobilization of Intracellular Tumor Necrosis Factor Alpha to the Surface of Mouse Peritoneal Neutrophils

Soumaya Bennouna, Woraporn Sukhumavasi, and Eric Y. Denkers^*

Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York

Received 26 September 2005/ Returned for modification 13 November 2005/ Accepted 2 May 2006

Neutrophils are well-known to rapidly respond to infection through chemotactic infiltration at sites of inflammation, followed by rapid release of microbicidal molecules, chemokines, and proinflammatory cytokines. For tumor necrosis factor alpha (TNF-), we recently found that neutrophils contain intracellular pools of the cytokine and display the capacity to upregulate transcriptional activity of the gene during lipopolysaccharide (LPS) stimulation. We now show that triggering of mouse peritoneal neutrophils with Toll-like receptor 2 (TLR2), TLR4, and TLR9 ligands, but not ligands of TLR3, induces upregulation of surface membrane TNF-. However, neutrophils infected with the protozoan Toxoplasma gondii displayed an inability to respond fully in terms of TLR ligand-induced increases in membrane TNF- expression. Infected neutrophils failed to display decreased levels of intracellular TNF- upon LPS exposure. In contrast to intermediate inhibitory effects in nontreated neutrophils, T. gondii induced a complete blockade in LPS-induced surface TNF- expression in the presence of the protein synthesis inhibitor cycloheximide. Despite these inhibitory effects, the parasite did not affect LPS-induced upregulation of TNF- gene transcription. Collectively, the results show that Toxoplasma prevents TLR ligand-triggered mobilization of TNF- to the neutrophil surface, revealing a novel immunosuppressive activity of the parasite.

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* Corresponding author. Mailing address: Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853-6401. Phone: (607) 253-4022. Fax: (607) 253-3384. E-mail: eyd1{at}cornell.edu.

Editor: J. F. Urban, Jr.

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Infection and Immunity, July 2006, p. 4274-4281, Vol. 74, No. 7
0019-9567/06/$08.00+0     doi:10.1128/IAI.01573-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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