Mite allergen is a danger signal for the skin via activation of inflammasome in keratinocytes
ABSTRACT Atopic dermatitis (AD) is a chronic inflammatory skin disorder caused by multiple factors. Among them, house dust mite (HDM) allergens are important in the development of AD. In airway allergy, HDM allergens activate innate immunity. However, information regarding the activation of innate immunity by HDM allergens in the skin is limited.
The inflammasome is a key regulator of pathogen recognition and inflammation. We investigated whether HDM allergens activate the inflammasome in epidermal keratinocytes.
Keratinocytes were stimulated with Dermatophagoides pteronyssinus, and the activation of caspase-1 and secretion of IL-1β and IL-18 were examined. Formation of the inflammasome was studied by analyzing the subcellular distributions of inflammasome proteins. The importance of specific inflammasome proteins was studied by knocking down their expression through transfection of keratinocytes with lentiviral particles carrying short hairpin RNAs (shRNAs).
D pteronyssinus activated caspase-1 and induced caspase-1-dependent release of IL-1β and IL-18 from keratinocytes. Moreover, D pteronyssinus stimulated assembly of the inflammasome by recruiting apoptosis-associated specklike protein containing a caspase-recruitment domain (ASC), caspase-1, and nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin-domain containing 3 (NLRP3) to the perinuclear region. Finally, infection with lentiviral particles carrying ASC, caspase-1, or NLRP3 shRNAs suppressed the release of IL-1β and IL-18 from the keratinocytes. Activation of the NLRP3 inflammasome by D pteronyssinus was dependent on cysteine protease activity.
House dust mite allergens are danger signals for the skin. In addition, HDM-induced activation of the NLRP3 inflammasome may play a pivotal role in the pathogenesis of AD.
- SourceAvailable from: Vishva Dixit
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- "The importance of inflammasome signaling to host defense responses is not limited to B. anthracis infection. The Nlrp3 inflammasome especially has been implicated in responses to a broad spectrum of infectious agents, including the bacterial pathogens S. aureus, Vibrio cholerae, Escherichia coli, Neisseria gonorrhoeae, Chlamydia pneumoniae, and Citrobacter rodentium (Duncan et al. 2009, He et al. 2010, Kayagaki et al. 2011, Shimada et al. 2011, Toma et al. 2010); the fungal pathogens Candida albicans and Aspergillus fumigatus (Gross et al. 2009, Hise et al. 2009, Joly et al. 2009, Said-Sadier et al. 2010); viral pathogens such as influenza A, encephalomyocarditis virus, and vesicular stomatitis virus (Allen et al. 2009, Ichinohe et al. 2010, Rajan et al. 2011, Thomas et al. 2009); and the parasites Schistosoma mansoni and Dermatophagoides pteronyssinus (Dai et al. 2011, Ritter et al. 2010). "
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