Toxoplasma gondii cyclophilin 18-mediated production of nitric oxide induces Bradyzoite conversion in a CCR5-dependent manner.
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.
Ibrahim
Hany M
HM
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
Bannai
Hiroshi
H
Xuan
Xuenan
X
Nishikawa
Yoshifumi
Y
D000818:Animals; D021983:Cyclophilins / Q000502:physiology*; D005260:Female; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000502:physiology*; D015800:Protozoan Proteins / Q000502:physiology*; D019713:Receptors, CCR5 / Q000502:physiology*; D014122:Toxoplasma / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D015800:Protozoan Proteins; D019713:Receptors, CCR5; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D021983:Cyclophilins