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S. M. Leal, Jr., Y. Sun, E. Pearlman; An Essential Role for Dectin 1 in the Pathogenesis of Aspergillus fumigatus Keratitis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2400.
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Dectin 1 is a C-type lectin receptor primarily expressed on macrophages and dendritic cells. Its ligand is the ubiquitous fungal cell wall constituent ß (1,3) glucan. Surface expression of ß-glucan depends on the stage of fungal development. For the filamentous fungal pathogen Aspergillus fumigatus , ß-glucan surface exposure is absent during the highly transmissible conidial stage (spore-form), but expressed constitutively upon germination and progression through the post-germination stages (swollen conidia, germ tube, and hyphal stages) of fungal development. This observation led us to hypothesize that Dectin 1 is involved in the innate immune recognition and the subsequent inflammatory response initiated upon germination of A.fumigatus conidia in fungal keratitis (corneal infection).
To address this hypothesis, we developed a mouse model in which 10^5 A. fumigatus conidia was injected into the corneal stroma of WT 129SvEv or Dectin 1-/- mice. The organisms were allowed to subsequently germinate, and clinical disease progression, neutrophil recruitment, & fungal viability assessed 24 Hr later.
Using this model, we identified a role for Dectin 1 in the recognition of the post-germination developmental stages of A.fumigatus, but not in response to resting conidia, which do not express ß-glucan. Clinical disease severity and neutrophilic infiltration was significantly reduced in Dectin 1-/- mice, though at the 24 Hr timepoint no difference in fungal survival was observed.
These data implicate a role for Dectin 1 in the pathogenesis of Aspergillus fumigatus keratitis, and gives credence to the potential therapeutic benefit of targeting the Dectin 1 signaling pathway in an effort to minimize the inflammatory-mediated corneal pathology during Aspergillus keratitis.
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