Source:http://linkedlifedata.com/resource/pubmed/id/17442959
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
2007-4-19
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pubmed: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.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD40,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interferon,
http://linkedlifedata.com/resource/pubmed/chemical/interferon gamma receptor
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
178
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5753-61
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pubmed:dateRevised |
2010-12-3
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pubmed:meshHeading |
pubmed-meshheading:17442959-Animals,
pubmed-meshheading:17442959-Antibodies, Monoclonal,
pubmed-meshheading:17442959-Antigens, CD40,
pubmed-meshheading:17442959-Brain,
pubmed-meshheading:17442959-CD4-Positive T-Lymphocytes,
pubmed-meshheading:17442959-Immunotherapy,
pubmed-meshheading:17442959-Interferon-gamma,
pubmed-meshheading:17442959-Interleukin-2,
pubmed-meshheading:17442959-Meningitis, Cryptococcal,
pubmed-meshheading:17442959-Mice,
pubmed-meshheading:17442959-Mice, Knockout,
pubmed-meshheading:17442959-Microglia,
pubmed-meshheading:17442959-RNA, Messenger,
pubmed-meshheading:17442959-Receptors, Interferon
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pubmed:year |
2007
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pubmed:articleTitle |
Protection from direct cerebral cryptococcus infection by interferon-gamma-dependent activation of microglial cells.
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pubmed:affiliation |
Division of Blood and Marrow Transplantation, Cancer Center and Department of Pediatrics, MMC 109, University of Minnesota, Minneapolis, MN 55455, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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