Infect Immun. 2011 Sep 12. [Epub ahead of print]
Toxoplasma gondii induces B7-2 expression through activation of JNK signal transduction
Morgado P, Ong YC, Boothroyd JC, Lodoen MB.
SourceDepartment of Molecular Biology and Biochemistry, 3238 McGaugh Hall, University of California, Irvine, Irvine, CA 92697.
Toxoplasma gondii is a globally distributed parasite pathogen that infects virtually all warm-blooded animals. A hallmark of immunity to acute infection is the production of IFN-γ and IL-12, followed by a protective T cell response that is critical for parasite control. Naïve T cell activation requires both TCR stimulation and the engagement of costimulatory receptors. Because of their important function in activating T cells, the expression of co-stimulatory ligands is believed to be under tight control. The molecular mechanisms governing their induction during microbial stimulation, however, are not well understood. We found that all three strains of T. gondii (Types I, II, and III) up-regulated the expression of B7-2, but not B7-1, on the surface of mouse bone marrow-derived macrophages. Additionally, intraperitoneal infection of mice with GFP-expressing parasites resulted in enhanced B7-2 levels specifically on infected, GFP(+)CD11b(+) cells. B7-2 induction occurred at the transcript level, required active parasite invasion, and was not dependent on MyD88 or TRIF. Functional assays demonstrated that T. gondii-infected macrophages stimulated naïve T cell proliferation in a B7-2-dependent manner. Genome-wide transcriptional analysis comparing infected and uninfected macrophages revealed the activation of MAPK signaling in infected cells. Using specific inhibitors against MAPKs, we determined that parasite-induced B7-2 is dependent on JNK, but not ERK or p38 signaling. We also observed that T. gondii-induced B7-2 expression on human peripheral blood monocytes is dependent on JNK signaling, indicating that a common mechanism of B7-2 regulation by T. gondii may exist in both humans and mice.
PMID:21911468[PubMed - as supplied by publisher]