ASC-Mediated Inflammation and Pyroptosis Attenuates Brucella abortus Pathogenesis Following the Recognition of gDNA

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dc.contributor.authorTupik, Juselyn D.en
dc.contributor.authorCoutermarsh-Ott, Sherylen
dc.contributor.authorBenton, Angela H.en
dc.contributor.authorKing, Kellie A.en
dc.contributor.authorKiryluk, Hanna D.en
dc.contributor.authorCaswell, Clayton C.en
dc.contributor.authorAllen, Irving C.en
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.contributor.departmentSchool of Medicineen
dc.date.accessioned2020-12-10T19:44:11Zen
dc.date.available2020-12-10T19:44:11Zen
dc.date.issued2020-11-30en
dc.date.updated2020-12-10T14:11:26Zen
dc.description.abstract<i>Brucella abortus</i> is a zoonotic pathogen that causes brucellosis. Because of <i>Brucella&rsquo;s</i> unique LPS layer and intracellular localization predominately within macrophages, it can often evade immune detection. However, pattern recognition receptors are capable of sensing <i>Brucella</i> pathogen-associated molecular patterns (PAMPS). For example, NOD-like receptors (NLRs) can form a multi-protein inflammasome complex to attenuate <i>Brucella</i> pathogenesis. The inflammasome activates IL-1&beta; and IL-18 to drive immune cell recruitment. Alternatively, inflammasome activation also initiates inflammatory cell death, termed pyroptosis, which augments bacteria clearance. In this report, we assess canonical and non-canonical inflammasome activation following <i>B. abortus</i> infection. We conducted in vivo studies using <i>Asc<sup>&minus;/&minus;</sup></i> mice and observed decreased mouse survival, immune cell recruitment, and increased bacteria load. We also conducted studies with <i>Caspase-11<sup>&minus;/&minus;</sup></i> mice and did not observe any significant impact on <i>B. abortus</i> pathogenesis. Through mechanistic studies using <i>Asc<sup>&minus;/&minus;</sup></i> macrophages, our data suggests that the protective role of ASC may result from the induction of pyroptosis through a gasdermin D-dependent mechanism in macrophages. Additionally, we show that the recognition of <i>Brucella</i> is facilitated by sensing the PAMP gDNA rather than the less immunogenic LPS. Together, these results refine our understanding of the role that inflammasome activation and pyroptosis plays during brucellosis.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationTupik, J.D.; Coutermarsh-Ott, S.L.; Benton, A.H.; King, K.A.; Kiryluk, H.D.; Caswell, C.C.; Allen, I.C. ASC-Mediated Inflammation and Pyroptosis Attenuates Brucella abortus Pathogenesis Following the Recognition of gDNA. Pathogens 2020, 9, 1008.en
dc.identifier.doihttps://doi.org/10.3390/pathogens9121008en
dc.identifier.urihttp://hdl.handle.net/10919/101069en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectbrucellosisen
dc.subjectcanonical inflammasomeen
dc.subjectnon-canonical inflammasomeen
dc.subjectNLRen
dc.subjectpyroptosisen
dc.subjectASCen
dc.subjectcaspase-11en
dc.subjectcaspase-1en
dc.subjectIL-1βen
dc.subjectgDNAen
dc.titleASC-Mediated Inflammation and Pyroptosis Attenuates Brucella abortus Pathogenesis Following the Recognition of gDNAen
dc.title.serialPathogensen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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