rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2010-11-26
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pubmed:abstractText |
The fact that some TLR-based vaccine adjuvants maintain function in TLR-deficient hosts highlights that their mechanism of function remains incompletely understood. Thus, we examined the ability of flagellin to induce cytokines and elicit/promote murine antibody responses upon deletion of the flagellin receptors TLR5 and/or NLRC4 (also referred to as IPAF) using a prime/boost regimen. In TLR5-KO mice, flagellin failed to induce NF-?B-regulated cytokines such as keratinocyte-derived chemokine (CXCL1) but induced WT levels of the inflammasome cytokine IL-18 (IL-1F4). Conversely, in NLRC4-KO mice, flagellin induced keratinocyte-derived chemokine, but not IL-18, whereas TLR5/NLRC4-DKO lacked induction of all cytokines measured. Flagellin/ovalbumin treatment resulted in high-antibody titers to both flagellin and ovalbumin in WT, TLR5-KO and DKO mice but did not elicit antibodies to either in TLR5/NLRC4-DKO mice. Thus, flagellin's ability to elicit/promote humoral immunity requires a germ-line-encoded receptor capable of recognizing this molecule. Such promotion of adaptive immunity can be effectively driven by either TLR5-mediated activation of NF-?B or NLRC4-mediated activation of the inflammasome.
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pubmed:grant |
|
pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
|
pubmed:status |
MEDLINE
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pubmed:month |
Dec
|
pubmed:issn |
1521-4141
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pubmed:author |
|
pubmed:issnType |
Electronic
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pubmed:volume |
40
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3528-34
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pubmed:dateRevised |
2011-5-18
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pubmed:meshHeading |
pubmed-meshheading:21072873-Animals,
pubmed-meshheading:21072873-Apoptosis Regulatory Proteins,
pubmed-meshheading:21072873-Calcium-Binding Proteins,
pubmed-meshheading:21072873-Cell Line,
pubmed-meshheading:21072873-Chemokine CXCL1,
pubmed-meshheading:21072873-Flagellin,
pubmed-meshheading:21072873-Host-Pathogen Interactions,
pubmed-meshheading:21072873-Immunity, Humoral,
pubmed-meshheading:21072873-Immunity, Innate,
pubmed-meshheading:21072873-Immunization,
pubmed-meshheading:21072873-Inflammasomes,
pubmed-meshheading:21072873-Interleukin-18,
pubmed-meshheading:21072873-Macrophages,
pubmed-meshheading:21072873-Mice,
pubmed-meshheading:21072873-Mice, Inbred C57BL,
pubmed-meshheading:21072873-Mice, Knockout,
pubmed-meshheading:21072873-NF-kappa B,
pubmed-meshheading:21072873-Signal Transduction,
pubmed-meshheading:21072873-Toll-Like Receptor 5
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pubmed:year |
2010
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pubmed:articleTitle |
TLR5 or NLRC4 is necessary and sufficient for promotion of humoral immunity by flagellin.
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pubmed:affiliation |
Department of Pathology, Emory University, Atlanta, GA 30322, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|