2008
DOI: 10.1038/gene.2008.23
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Susceptibility to Coccidioides species in C57BL/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a)

Abstract: 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-… Show more

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Cited by 69 publications
(64 citation statements)
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“…This phenomenon has been previously demonstrated for infections with A. fumigatus 5 and Coccidioides spp., 20 in which the mechanisms of antifungal resistance were to some extent determined by the host's genetics. It has been suggested that dectin-1 responses may be dependent on the fungal strains 1 and on the physical status of the b-glucans (soluble or particulate).…”
Section: Discussionmentioning
confidence: 99%
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“…This phenomenon has been previously demonstrated for infections with A. fumigatus 5 and Coccidioides spp., 20 in which the mechanisms of antifungal resistance were to some extent determined by the host's genetics. It has been suggested that dectin-1 responses may be dependent on the fungal strains 1 and on the physical status of the b-glucans (soluble or particulate).…”
Section: Discussionmentioning
confidence: 99%
“…The contribution of dectin-1-mediated mechanisms of antifungal resistance was indeed found to depend to some extent on the genetic background of the host. 5,20 Macrophages from BALB/c and genetically related strains have been reported to express the full-length dectin-1A and the stalkless dectin-1B isoforms at comparable levels, whereas macrophages from the C57BL/6 background and related mice predominantly expressed the smaller isoform. 21 The results of the present study demonstrate that the functional activity of dectin-1 in both gastrointestinal and vaginal candidiasis is contingent upon the host's genetic background and affects both innate cytokine production, as well as the adaptive Th1/ Th17 cell activation.…”
Section: Introductionmentioning
confidence: 99%
“…It is generally accepted that that the innate immune response determines the nature of the adaptive immune response, and that is also true in experimental coccidioidomycosis. DBA/2, a highly resistant mouse strain makes more IL-12p70, IL-23p19, IFNγ, Stat1, and IL-17a and less IL-10 after infection compared to highly susceptible strains, both in vivo and in vitro [58,59]. In mice, increased IL-10 production results in increased susceptibility, and conversely, IL-10 KO mice are more resistant than the susceptible parental strain, closely resembling DBA/2, the most resistant inbred strain [60].…”
Section: Immunologymentioning
confidence: 99%
“…The only known driver of those differences in mice is Dectin-1, the β glucan receptor, which is expressed on dendritic and other myeloid cells [61]. There is a difference in the structure and function of Dectin-1 in susceptible B6 mice and resistant DBA/2 mice that is based on alternative splicing of the encoding gene, Clec7a [59]. That gene is also alternatively spliced in human cells [62,63], but there are no studies on how that differential splicing affects the human response to spherules.…”
Section: Immunologymentioning
confidence: 99%
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