Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-1-3
pubmed:abstractText
Cytosine-phosphate-guanosine-containing oligodeoxynucleotides (CpG ODN) are important vaccine adjuvants that promote Th1-type immune responses. Cryptococcus neoformans is a serious human pathogen that replicates in the lung but may disseminate systemically leading to meningitis, particularly in immunocompromised individuals. Immunization of susceptible C57BL/6 mice with CpG ODN deviates the immune response from a Th2- toward a Th1-type response following infection with C. neoformans. CpG also induces IL-12, TNF, MCP-1 and macrophage nitric oxide production. CD4(+) and CD8(+) T cells producing IFN-gamma increase in frequency, while those producing IL-5 decrease. More importantly, pulmonary eosinophilia is significantly reduced, an effect that depends on IL-12 and CD8(+) T cells but not NK cells. CpG treatment also reduces the burden of C. neoformans in the lung, an effect that is IL-12-, NK cell- and T cell-independent and probably reflects a direct effect of CpG on pathogen opsonization or an enhancement of macrophage antimicrobial activity. An equivalent beneficial effect is also observed when CpG ODN treatment is delivered during established cryptococcal disease. This is the first study documenting that promotion of lung TLR9 signaling using synthetic agonists enhances host defense. Activation of innate immunity has clear therapeutic potential and may even be beneficial in patients with acquired immune deficiency.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
273-81
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15597328-Adjuvants, Immunologic, pubmed-meshheading:15597328-Animals, pubmed-meshheading:15597328-Cryptococcosis, pubmed-meshheading:15597328-Cryptococcus neoformans, pubmed-meshheading:15597328-Cytokines, pubmed-meshheading:15597328-DNA-Binding Proteins, pubmed-meshheading:15597328-Eosinophilia, pubmed-meshheading:15597328-Female, pubmed-meshheading:15597328-Immunity, Innate, pubmed-meshheading:15597328-Interleukin-12, pubmed-meshheading:15597328-Lung, pubmed-meshheading:15597328-Lung Diseases, Fungal, pubmed-meshheading:15597328-Mice, pubmed-meshheading:15597328-Mice, Inbred C57BL, pubmed-meshheading:15597328-Mice, Knockout, pubmed-meshheading:15597328-Oligodeoxyribonucleotides, pubmed-meshheading:15597328-Receptors, Cell Surface, pubmed-meshheading:15597328-Th1 Cells, pubmed-meshheading:15597328-Th2 Cells, pubmed-meshheading:15597328-Toll-Like Receptor 9
pubmed:year
2005
pubmed:articleTitle
Stimulation via Toll-like receptor 9 reduces Cryptococcus neoformans-induced pulmonary inflammation in an IL-12-dependent manner.
pubmed:affiliation
Department of Biological Sciences, Imperial College London, CMMI, London SW7 2AZ, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't