title: Overproduction of Toxoplasma gondii cyclophilin-18 regulates host cell migration and enhances parasite dissemination in a CCR5-independent manner.
abstract: BACKGROUND
  Toxoplasma gondii hijacks host cells to allow it to disseminate throughout a host animal; however, the migratory machinery involved in this process has not been well characterized. We examined the functional role of T. gondii cyclophilin 18 (TgCyp18) in host cell recruitment using recombinant parasites transfected with TgCyp18.
  
  
  RESULTS
  High levels of TgCyp18 enhanced IL-12 production in cysteine-cysteine chemokine receptor 5 (CCR5) knockout mice (CCR5-/-) that had been infected peritoneally with T. gondii. Recruitment of CD11b+ cells to the infection site was enhanced in a CCR5-independent manner. T. gondii spread to several organs, particularly the liver, in a TgCyp18-dependent and CCR5-independent manner. Additionally, CCL5 levels were upregulated in macrophages treated with recombinant protein TgCyp18 and in the peritoneal fluids of the infected CCR5-/- mice. Furthermore, the chemokines involved in macrophage migration, CCL2 and CXCL10, were upregulated in the livers of CCR5-/- mice infected with recombinant parasites that had been transfected with TgCyp18.
  
  
  CONCLUSIONS
  TgCyp18 may play a crucial role in macrophage migration, and in assisting with transport of T. gondii via CCR5-independent mechanisms. TgCyp18 may also play a role with CCL5 in the migration of macrophages to the site of infection, and with CCL2 and CXCL10 in the transport of T. gondii-infected cells to the liver.
authors.forename: Hany M
authors.initials: HM
authors.lastname: Ibrahim
authors.forename: Maki
authors.initials: M
authors.lastname: Nishimura
authors.forename: Sachi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Walaa
authors.initials: W
authors.lastname: Awadin
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Furuoka
authors.forename: Xuenan
authors.initials: X
authors.lastname: Xuan
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan. nisikawa@obihiro.ac.jp.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nishikawa
mesh_terms: D000818:Animals; D002465:Cell Movement; D021983:Cyclophilins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D008264:Macrophages / Q000469:parasitology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019713:Receptors, CCR5 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D014122:Toxoplasma / Q000235:genetics* / Q000502:physiology
chemical_list: D019713:Receptors, CCR5; D011994:Recombinant Proteins; D021983:Cyclophilins