Linked Life Data

18641352

Source:http://linkedlifedata.com/resource/pubmed/id/18641352

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-7-21
pubmed:abstractText
Adenovirus (Ad) vectors are promising candidates for both gene transfer and vaccine applications. In this study, we investigated the role of TLR2 in innate and adaptive immune responses to Ad and/or the transgene it expresses following systemic injection. We found that Ad directly activates ERK1/2 in vivo, but that initiation of ERK1/2 activation is primarily a MyD88/TLR2-independent, but Kupffer cell-dependent, event. The complexity of Ad-induced innate immune responses was confirmed when we also found that both TLR2 and MyD88 functions are required for the sustained activation of ERK1/2. Although we found that the initial activation of NF-kappaB by Ads is dependent upon MyD88, but independent of TLR2 in (non-Kupffer cells) the liver, TLR2 significantly influenced the Ad-induced late phase NF-kappaB activation. These very rapid responses were positively correlated with subsequent innate immune responses to the Ad vector, as our results confirmed that the induction of several cytokines and chemokines, and the expression of innate immune response genes following Ad injection were TLR2 dependent in vivo. The requirement of TLR2 in Ad-induced innate responses also correlated with significantly altered adaptive immune responses. For example, our results demonstrate that the generation of Ad-neutralizing Abs, and anti-transgene-specific Abs elicited subsequent to Ad vector treatments, are both dependent upon TLR2 functionality. Finally, we found that several Ad-induced innate immune responses are dependent on both TLR2 and TLR9. Therefore, this study confirms that several (but not all) Ad-induced innate and adaptive immune responses are TLR dependent.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
181
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2134-44
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18641352-Adaptation, Physiological, pubmed-meshheading:18641352-Adenoviridae, pubmed-meshheading:18641352-Animals, pubmed-meshheading:18641352-Antibodies, pubmed-meshheading:18641352-Cells, Cultured, pubmed-meshheading:18641352-Cytokines, pubmed-meshheading:18641352-Enzyme Activation, pubmed-meshheading:18641352-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:18641352-Gene Expression Regulation, pubmed-meshheading:18641352-Genetic Vectors, pubmed-meshheading:18641352-Immunity, Innate, pubmed-meshheading:18641352-Kupffer Cells, pubmed-meshheading:18641352-Liver, pubmed-meshheading:18641352-MAP Kinase Signaling System, pubmed-meshheading:18641352-Macrophages, pubmed-meshheading:18641352-Mice, pubmed-meshheading:18641352-Mice, Knockout, pubmed-meshheading:18641352-Myeloid Differentiation Factor 88, pubmed-meshheading:18641352-Toll-Like Receptor 2, pubmed-meshheading:18641352-Toll-Like Receptor 9
pubmed:year
2008
pubmed:articleTitle
Adenovirus vector-induced innate inflammatory mediators, MAPK signaling, as well as adaptive immune responses are dependent upon both TLR2 and TLR9 in vivo.
pubmed:affiliation
Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural