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Infection and Immunity, September 2009, p. 3686-3695, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00361-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Toxoplasma gondii Cyclophilin 18-Mediated Production of Nitric Oxide Induces Bradyzoite Conversion in a CCR5-Dependent Manner{triangledown}

Hany M. Ibrahim,1,2 Hiroshi Bannai,1 Xuenan Xuan,1 and Yoshifumi Nishikawa1*

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan,1 Zoology Department, Faculty of Science, Minufiya University, Shibin El kom, Egypt2

Received 30 March 2009/ Returned for modification 16 May 2009/ Accepted 18 June 2009

Toxoplasma gondii modulates pro- and anti-inflammatory responses to regulate parasite multiplication and host survival. Pressure from the immune response causes the conversion of tachyzoites into slowly dividing bradyzoites. The regulatory mechanisms involved in this switch are poorly understood. The aim of this study was to investigate the immunomodulatory role of T. gondii cyclophilin 18 (TgCyp18) in macrophages and the consequences of the cellular responses on the conversion machinery. Recombinant TgCyp18 induced the production of nitric oxide (NO), interleukin-12 (IL-12), and tumor necrosis factor alpha through its binding with cysteine-cysteine chemokine receptor 5 (CCR5) and the production of gamma interferon and IL-6 in a CCR5-independent manner. Interestingly, the treatment of macrophages with TgCyp18 resulted in the inhibition of parasite growth and an enhancement of the conversion into bradyzoites via NO in a CCR5-dependent manner. In conclusion, T. gondii possesses sophisticated mechanisms to manipulate host cell responses in a TgCyp18-mediated process.


* Corresponding author. Mailing address: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan. Phone: 81-155-49-5886. Fax: 81-155-49-5643. E-mail: nisikawa{at}obihiro.ac.jp

{triangledown} Published ahead of print on 29 June 2009.

Editor: W. A. Petri, Jr.


Infection and Immunity, September 2009, p. 3686-3695, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00361-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.