ASC-Mediated Inflammation and Pyroptosis Attenuates Brucella abortus Pathogenesis Following the Recognition of gDNA.
Pathogens
; 9(12)2020 Nov 30.
Article
in En
| MEDLINE
| ID: mdl-33266295
ABSTRACT
Brucella abortus is a zoonotic pathogen that causes brucellosis. Because of Brucella's unique LPS layer and intracellular localization predominately within macrophages, it can often evade immune detection. However, pattern recognition receptors are capable of sensing Brucella pathogen-associated molecular patterns (PAMPS). For example, NOD-like receptors (NLRs) can form a multi-protein inflammasome complex to attenuate Brucella pathogenesis. The inflammasome activates IL-1ß 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 B. abortus infection. We conducted in vivo studies using Asc-/- mice and observed decreased mouse survival, immune cell recruitment, and increased bacteria load. We also conducted studies with Caspase-11-/- mice and did not observe any significant impact on B. abortus pathogenesis. Through mechanistic studies using Asc-/- 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 Brucella 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Etiology_studies
Language:
En
Journal:
Pathogens
Year:
2020
Document type:
Article
Affiliation country: