| First Author | Zhou Q | Year | 2007 |
| Journal | J Immunol | Volume | 178 |
| Issue | 9 | Pages | 5753-61 |
| PubMed ID | 17442959 | Mgi Jnum | J:145833 |
| Mgi Id | MGI:3836128 | Doi | 10.4049/jimmunol.178.9.5753 |
| Citation | Zhou Q, et al. (2007) Protection from direct cerebral cryptococcus infection by interferon-gamma-dependent activation of microglial cells. J Immunol 178(9):5753-61 |
| abstractText | The brain represents a significant barrier for protective immune responses in both infectious disease and cancer. We have recently demonstrated that immunotherapy with anti-CD40 and IL-2 can protect mice against disseminated Cryptococcus infection. We now applied this immunotherapy using a direct cerebral cryptococcosis model to study direct effects in the brain. Administration of anti-CD40 and IL-2 significantly prolonged the survival time of mice infected intracerebrally with Cryptococcus neoformans. The protection was correlated with activation of microglial cells indicated by the up-regulation of MHC II expression on brain CD45(low)CD11b(+) cells. CD4(+) T cells were not required for either the microglial cell activation or anticryptococcal efficacy induced by this immunotherapy. Experiments with IFN-gamma knockout mice and IFN-gammaR knockout mice demonstrated that IFN-gamma was critical for both microglial cell activation and the anticryptococcal efficacy induced by anti-CD40/IL-2. Interestingly, while peripheral IFN-gamma production and microglial cell activation were observed early after treatment, negligible IFN-gamma was detected locally in the brain. These studies indicate that immunotherapy using anti-CD40 and IL-2 can augment host immunity directly in the brain against C. neoformans infection and that IFN-gamma is essential for this effect. |
