ASC-Mediated Inflammation and Pyroptosis Attenuates Brucella abortus Pathogenesis Following the Recognition of gDNA
| dc.contributor.author | Tupik, Juselyn D. | en |
| dc.contributor.author | Coutermarsh-Ott, Sheryl | en |
| dc.contributor.author | Benton, Angela H. | en |
| dc.contributor.author | King, Kellie A. | en |
| dc.contributor.author | Kiryluk, Hanna D. | en |
| dc.contributor.author | Caswell, Clayton C. | en |
| dc.contributor.author | Allen, Irving C. | en |
| dc.contributor.department | Biomedical Sciences and Pathobiology | en |
| dc.contributor.department | School of Medicine | en |
| dc.date.accessioned | 2020-12-10T19:44:11Z | en |
| dc.date.available | 2020-12-10T19:44:11Z | en |
| dc.date.issued | 2020-11-30 | en |
| dc.date.updated | 2020-12-10T14:11:26Z | en |
| dc.description.abstract | <i>Brucella abortus</i> is a zoonotic pathogen that causes brucellosis. Because of <i>Brucella’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-1β 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>−/−</sup></i> mice and observed decreased mouse survival, immune cell recruitment, and increased bacteria load. We also conducted studies with <i>Caspase-11<sup>−/−</sup></i> mice and did not observe any significant impact on <i>B. abortus</i> pathogenesis. Through mechanistic studies using <i>Asc<sup>−/−</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.version | Published version | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.citation | Tupik, 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.doi | https://doi.org/10.3390/pathogens9121008 | en |
| dc.identifier.uri | http://hdl.handle.net/10919/101069 | en |
| dc.language.iso | en | en |
| dc.publisher | MDPI | en |
| dc.rights | Creative Commons Attribution 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en |
| dc.subject | brucellosis | en |
| dc.subject | canonical inflammasome | en |
| dc.subject | non-canonical inflammasome | en |
| dc.subject | NLR | en |
| dc.subject | pyroptosis | en |
| dc.subject | ASC | en |
| dc.subject | caspase-11 | en |
| dc.subject | caspase-1 | en |
| dc.subject | IL-1β | en |
| dc.subject | gDNA | en |
| dc.title | ASC-Mediated Inflammation and Pyroptosis Attenuates Brucella abortus Pathogenesis Following the Recognition of gDNA | en |
| dc.title.serial | Pathogens | en |
| dc.type | Article - Refereed | en |
| dc.type.dcmitype | Text | en |