Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-6-4
pubmed:abstractText
Coccidioides posadasii spherules stimulate macrophages to make cytokines via TLR-2 and Dectin-1. We used formalin-killed spherules and 1,3-beta-glucan purified from spherules to stimulate elicited peritoneal macrophages and myeloid dendritic cells (mDCs) from susceptible (C57BL/6) and resistant (DBA/2) mouse strains. DBA/2 macrophages produced more TNF-alpha and IL-6 than macrophages from C57BL/6 mice, and the amount of TNF-alpha made was dependent on both TLR2 and Dectin-1. DCs from C57BL/6 mice made more IL-10 and less IL-23p19 and IL-12p70 than did DBA/2 DC. These responses were inhibited by a monoclonal antibody to Dectin-1. DBA/2 mice expressed full-length Dectin-1, whereas C57BL/6 mice spliced out exon 3, which encodes most of the stalk. RAW cells transduced to express the full-length Dectin-1 responded better to FKS than cells expressing truncated Dectin-1. We compared the isoform of Dectin-1 expressed by 34 C57BL/6 X DBA/2 recombinant inbred (BXD RI) lines with their susceptibility to Coccidioides immitis. In 25 of 34 RI lines susceptibility or resistance corresponded to short or full-length isoforms, respectively. These results suggest that alternative splicing of the Dectin-1 gene contributes to susceptibility of C57BL/6 mice to coccidioidomycosis, and affects the cytokine responses of macrophages and mDCs to spherules.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1476-5470
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
338-48
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed-meshheading:18418396-Alternative Splicing, pubmed-meshheading:18418396-Animals, pubmed-meshheading:18418396-Cell Line, pubmed-meshheading:18418396-Coccidioides, pubmed-meshheading:18418396-Coccidioidomycosis, pubmed-meshheading:18418396-Dendritic Cells, pubmed-meshheading:18418396-Gene Expression, pubmed-meshheading:18418396-Genetic Predisposition to Disease, pubmed-meshheading:18418396-Immunity, Innate, pubmed-meshheading:18418396-Interleukin-10, pubmed-meshheading:18418396-Macrophages, Peritoneal, pubmed-meshheading:18418396-Membrane Proteins, pubmed-meshheading:18418396-Mice, pubmed-meshheading:18418396-Mice, Inbred C57BL, pubmed-meshheading:18418396-Mice, Inbred DBA, pubmed-meshheading:18418396-Nerve Tissue Proteins, pubmed-meshheading:18418396-Protein Isoforms, pubmed-meshheading:18418396-Species Specificity, pubmed-meshheading:18418396-Tumor Necrosis Factor-alpha
pubmed:year
2008
pubmed:articleTitle
Susceptibility to Coccidioides species in C57BL/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a).
pubmed:affiliation
Research Service, VA San Diego Healthcare, San Diego, CA 92161, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't