Protection from direct cerebral Cryptococcus infection by interferon-γ-dependent activation of microglial cells

Qing Zhou, Ruth A. Gault, Thomas R. Kozel, William J Murphy

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

The brain represents a significant barrier for protective immune responses in both infections 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 CD45lowCD11b+ cells. CD4+ T cells were not required for either the microglial cell activation or anticryptococcal efficacy induced by this immunotherapy. Experiments with IFN-γ knockout mice and IFN-γR knockout mice demonstrated that IFN-γ was critical for both microglial cell activation and the anticryptococcal efficacy induced by anti-CD40/IL-2. Interestingly, while peripheral IFN-γ production and microglial cell activation were observed early after treatment, negligible IFN-γ 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-γ is essential for this effect.

Original languageEnglish (US)
Pages (from-to)5753-5761
Number of pages9
JournalJournal of Immunology
Volume178
Issue number9
StatePublished - May 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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