Toxoplasma gondii cyclophilin 18-mediated production of nitric oxide induces bradyzoite conversion in a CCR5-dependent manner

Infect Immun. 2009 Jun 29. [Epub ahead of print]

Toxoplasma gondii cyclophilin 18-mediated production of nitric oxide induces bradyzoite conversion in a CCR5-dependent manner

Ibrahim HM, Bannai H, Xuan X, Nishikawa Y.

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

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 to 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 cyclophilin18 (TgCyp18) in macrophages and the consequences of the cellular responses on the conversion machinery. The recombinant TgCyp18 induced the production of nitric oxide (NO), IL-12 and TNF-alpha through its binding with cysteine-cysteine chemokine receptor 5 (CCR5) and the production of IFN-gamma and IL-6 in a CCR5-independent manner. Interestingly, treatment of macrophages with TgCyp18 resulted in the inhibition of parasite growth and 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.

PMID: 19564392 [PubMed - as supplied by publisher]