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HPV16 activates the AIM2 inflammasome in keratinocytes | Archives of Dermatological Research
Description:
Human papillomaviruses (HPV) are double-stranded DNA viruses, which selectively infect keratinocytes in stratified epithelia. After an initial infection, many patients clear HPV. In some patients, however, HPV persist, and dysfunctional innate immune responses to HPV infection could be involved in the ineffective clearing of these viruses. In this study, the mechanisms of HPV-induced immune responses in keratinocytes were investigated. Binding of viral DNA leads to AIM2 inflammasome activation and IL-1β release, while IFI16 activation results in IFN-β release. Using immunohistochemistry, AIM2 and IFI16—two recently identified sensors for cytosolic DNA—were also detected in HPV positive skin lesions. CISH stainings further confirmed the presence of cytosolic HPV16 DNA in biopsy samples. Moreover, active IL-1β and cleaved caspase-1 were detected in HPV infected skin, suggesting inflammasome activation by viral DNA. In subsequent functional studies, HPV16 DNA triggered IL-1β and IL-18 release via the AIM2 inflammasome in normal human keratinocytes. Although HPV DNA did not induce IFN-β in keratinocytes, IFN-β secretion was observed when AIM2 was blocked. Meanwhile, blocking of IFI16 increased HPV16 DNA-induced IL-1β, but not IL-18, secretion. These findings suggest crosstalk between IFI16 and AIM2 in the immune response to HPV DNA. In sum, novel aspects concerning HPV-induced innate immune responses were identified. Eventually, understanding the mechanisms of HPV-induced inflammasome activation could lead to the development of novel strategies for the prevention and treatment of HPV infections.
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article, google, scholar, pubmed, cas, hpv, inflammasome, human, dna, aim, infection, immune, keratinocytes, ifi, papillomavirus, responses, immunol, activation, access, hornung, cell, privacy, cookies, content, research, viruses, ilβ, cytosolic, response, virus, dermatol, cancer, fitzgerald, supplementary, material, publish, search, kreuter, schauber, innate, secretion, open, protein, ablasser, interleukinbeta, biol, rev, med, anal, interferon,
Topics {✒️}
month download article/chapter virus activates interleukin-1beta cell-dependent skin inflammation hpv-induced inflammasome activation hpv-induced immune responses double-stranded dna viruses human papilloma viruses ultraviolet b-exposed keratinocytes eliminating ano-genital cancer intracellular dna-sensing pathways int/vaccines/en/hpvrd active il-1β cytosolic hpv16 dna il-1β release dermatological research aims recently identified sensors related subjects ifi16 protein mediates full article pdf privacy choices/manage cookies innate immune sensing nuclear protein ifi16 innate immune sensor e1 protein regulates suggesting inflammasome activation adaptive immune responses aim2 inflammasome activation hiv-positive men 789 hpv-positive women hpv infected skin viral dna leads van ommen gj cellular network comprising immune response human papillomavirus infection ifn-β secretion human papillomavirus types human papillomavirus deregulates epithelial cell responses hpv16 activates article archives european economic area scope submit manuscript subsequent functional studies findings suggest crosstalk nuclear pathogen sensor penile intraepithelial neoplasia fritz thyssen stiftung kroener fresenius stiftung ludwig-maximilian-university
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headline:HPV16 activates the AIM2 inflammasome in keratinocytes
description:Human papillomaviruses (HPV) are double-stranded DNA viruses, which selectively infect keratinocytes in stratified epithelia. After an initial infection, many patients clear HPV. In some patients, however, HPV persist, and dysfunctional innate immune responses to HPV infection could be involved in the ineffective clearing of these viruses. In this study, the mechanisms of HPV-induced immune responses in keratinocytes were investigated. Binding of viral DNA leads to AIM2 inflammasome activation and IL-1β release, while IFI16 activation results in IFN-β release. Using immunohistochemistry, AIM2 and IFI16—two recently identified sensors for cytosolic DNA—were also detected in HPV positive skin lesions. CISH stainings further confirmed the presence of cytosolic HPV16 DNA in biopsy samples. Moreover, active IL-1β and cleaved caspase-1 were detected in HPV infected skin, suggesting inflammasome activation by viral DNA. In subsequent functional studies, HPV16 DNA triggered IL-1β and IL-18 release via the AIM2 inflammasome in normal human keratinocytes. Although HPV DNA did not induce IFN-β in keratinocytes, IFN-β secretion was observed when AIM2 was blocked. Meanwhile, blocking of IFI16 increased HPV16 DNA-induced IL-1β, but not IL-18, secretion. These findings suggest crosstalk between IFI16 and AIM2 in the immune response to HPV DNA. In sum, novel aspects concerning HPV-induced innate immune responses were identified. Eventually, understanding the mechanisms of HPV-induced inflammasome activation could lead to the development of novel strategies for the prevention and treatment of HPV infections.
datePublished:2013-06-14T00:00:00Z
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AIM2
HPV16
IL-1β
IFI16
DNA sensors
Dermatology
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headline:HPV16 activates the AIM2 inflammasome in keratinocytes
description:Human papillomaviruses (HPV) are double-stranded DNA viruses, which selectively infect keratinocytes in stratified epithelia. After an initial infection, many patients clear HPV. In some patients, however, HPV persist, and dysfunctional innate immune responses to HPV infection could be involved in the ineffective clearing of these viruses. In this study, the mechanisms of HPV-induced immune responses in keratinocytes were investigated. Binding of viral DNA leads to AIM2 inflammasome activation and IL-1β release, while IFI16 activation results in IFN-β release. Using immunohistochemistry, AIM2 and IFI16—two recently identified sensors for cytosolic DNA—were also detected in HPV positive skin lesions. CISH stainings further confirmed the presence of cytosolic HPV16 DNA in biopsy samples. Moreover, active IL-1β and cleaved caspase-1 were detected in HPV infected skin, suggesting inflammasome activation by viral DNA. In subsequent functional studies, HPV16 DNA triggered IL-1β and IL-18 release via the AIM2 inflammasome in normal human keratinocytes. Although HPV DNA did not induce IFN-β in keratinocytes, IFN-β secretion was observed when AIM2 was blocked. Meanwhile, blocking of IFI16 increased HPV16 DNA-induced IL-1β, but not IL-18, secretion. These findings suggest crosstalk between IFI16 and AIM2 in the immune response to HPV DNA. In sum, novel aspects concerning HPV-induced innate immune responses were identified. Eventually, understanding the mechanisms of HPV-induced inflammasome activation could lead to the development of novel strategies for the prevention and treatment of HPV infections.
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AIM2
HPV16
IL-1β
IFI16
DNA sensors
Dermatology
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