Predominant Interferon-gamma-Mediated Expression of CXCL9, CXCL10, and CCL5 Proteins in the Brain During Chronic Infection with Toxoplasma

J Interferon Cytokine Res. 2010 Jul 13. [Epub ahead of print]

Predominant Interferon-gamma-Mediated Expression of CXCL9, CXCL10, and CCL5 Proteins in the Brain During Chronic Infection with Toxoplasma gondii in BALB/c Mice Resistant to Development of Toxoplasmic Encephalitis

Wen X, Kudo T, Payne L, Wang X, Rodgers L, Suzuki Y.

1 Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University , Blacksburg, Virginia.

Abstract
We examined the role of interferon-gamma (IFN-gamma) in expression of chemokine mRNA and proteins in the brain during chronic infection with Toxoplasma gondii using BALB/c and BALB/c-background IFN-gamma knockout (IFN-gamma(-/-)) mice. BALB/c mice are genetically resistant to development of toxoplasmic encephalitis and establish a latent, chronic infection in the brain through IFN-gamma-mediated immune responses. Amounts of mRNA for CXCL9/MIG, CXCL10/IP-10, CXCL11/I-TAC, CCL2/MCP-1, CCL3/MIP-1alpha, and CCL5/RANTES significantly increased in the brains of wild-type mice after infection. CXCL9/MIG, CXCL10/IP-10, and CCL5/RANTES mRNA were most abundant among these chemokines. An increase in amounts of mRNA for CXCL10/IP-10, CCL2/MCP-1, CCL3/MIP-1alpha, and CCL5/RANTES was also observed in the brains of IFN-gamma(-/-) mice after infection, although CXCL10/I-10 and CCL5/RANTES mRNA levels in infected IFN-gamma(-/-) mice were significantly lower than those of infected wild-type animals. Amounts of mRNA for CXCL9/MIG and CXCL11/I-TAC remained at the basal levels in infected IFN-gamma(-/-) mice. When amounts of the chemokine proteins were examined in the brain homogenates of uninfected and infected mice of both strains, large amounts of CXCL9/MIG, CXCL10/IP-10, and CCL5/RANTES were detected only in infected wild-type animals. These results indicate that CXCL9/MIG, CXCL10/IP-10, and CCL5/RANTES are the chemokines predominantly induced in the brains of genetically resistant BALB/c mice during chronic infection with T. gondii, and their expression is dependent on IFN-gamma.

PMID: 20626297 [PubMed - as supplied by publisher]