Open AccessToxoplasma gondiiCyclophilin 18-Mediated Production of Nitric Oxide Induces Bradyzoite Conversion in a CCR5-Dependent Manner
Author(s) -
Hany M. Ibrahim,
Hiroshi Bannai,
Xuenan Xuan,
Yoshifumi Nishikawa
Publication year - 2009
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00361-09
Subject(s) - toxoplasma gondii , biology , nitric oxide , chemokine , microbiology and biotechnology , immune system , interferon gamma , tumor necrosis factor alpha , recombinant dna , immunology , biochemistry , antibody , gene , endocrinology
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 ofT. 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.