Toxoplasma GRA15 expression on dendritic cells inhibits B cell differentiation and antibody production.

Abstract

One of the dense granule proteins named GRA15 in Toxoplasma gondii (T. gondii), is known to support an innate immune response in host through activation of NF-κB. However, little is known about advantages of GRA15 for parasites. By examining the role of GRA15 in the host-parasite interactions, it was clarified that GRA15 in T. gondii suppressed acquired immune responses in host. Wild-type parasite infection to C57BL/6 mice resulted in lower titers of T. gondii antibody and lower plasma cell counts compared to Δgra15 T. gondii. To identify host cells in which GRA15 acts to suppress antibody production, we generated conditional knock-in mice that express GRA15 in specific cell lineages. Anti-T. gondii antibodies were not reduced in macrophages of conditional knock-in mice after infection with Δgra15 T. gondii, while the production of T. gondii antibody was suppressed in dendritic cells of the conditional knock-in mice (CD11c-Cre/GRA15cKI). In the CD11c-Cre/GRA15cKI immunized with ovalbumin (OVA), the titers of anti-OVA antibody were reduced compared to control mice. Furthermore, the number of OVA antigen-specific T cells was also decreased in CD11c-Cre/GRA15cKI. These data showed that GRA15 in dendritic cells suppressed T cell-mediated humoral immunity. These findings might implicate the pathological significance of GRA15 and facilitate Toxoplasma vaccines production.