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 language | English (US) |
|---|---|
| Pages (from-to) | 5753-5761 |
| Number of pages | 9 |
| Journal | Journal of Immunology |
| Volume | 178 |
| Issue number | 9 |
| State | Published - May 1 2007 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
Protection from direct cerebral Cryptococcus infection by interferon-γ-dependent activation of microglial cells. / Zhou, Qing; Gault, Ruth A.; Kozel, Thomas R.; Murphy, William J.
In: Journal of Immunology, Vol. 178, No. 9, 01.05.2007, p. 5753-5761.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Protection from direct cerebral Cryptococcus infection by interferon-γ-dependent activation of microglial cells
AU - Zhou, Qing
AU - Gault, Ruth A.
AU - Kozel, Thomas R.
AU - Murphy, William J
PY - 2007/5/1
Y1 - 2007/5/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=34247554871&partnerID=8YFLogxK
M3 - Article
C2 - 17442959
AN - SCOPUS:34247554871
VL - 178
SP - 5753
EP - 5761
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 9
ER -