Format

Send to

Choose Destination
Infect Immun. 2018 Aug 22;86(9). pii: e00361-18. doi: 10.1128/IAI.00361-18. Print 2018 Sep.

Caspase-1 and Caspase-11 Mediate Pyroptosis, Inflammation, and Control of Brucella Joint Infection.

Author information

1
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA.
2
Laboratory for Infectious Disease Research, University of Missouri, Columbia, Missouri, USA.
3
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA skybergj@missouri.edu.

Abstract

Brucellosis, caused by the intracellular bacterial pathogen Brucella, is a zoonotic disease for which arthritis is the most common focal complication in humans. Here we investigated the role of inflammasomes and their effectors, including interleukin-1 (IL-1), IL-18, and pyroptosis, on inflammation and control of infection during Brucella-induced arthritis. Early in infection, both caspase-1 and caspase-11 were found to initiate joint inflammation and proinflammatory cytokine production. However, by 1 week postinfection, caspase-1 and caspase-11 also contributed to control of Brucella joint infection. Inflammasome-dependent restriction of Brucella joint burdens did not require AIM2 (absent in melanoma 2) or NLRP3 (NLR family, pyrin domain containing 3). IL-1R had a modest effect on Brucella-induced joint swelling, but mice lacking IL-1R were not impaired in their ability to control infection of the joint by Brucella In contrast, IL-18 contributed to the initiation of joint swelling and control of joint Brucella infection. Caspase1/11-dependent cell death was observed in vivo, and in vitro studies demonstrated that both caspase-1 and caspase-11 induce pyroptosis, which limited Brucella infection in macrophages. Brucella lipopolysaccharide alone was also able to induce caspase-11-dependent pyroptosis. Collectively, these data demonstrate that inflammasomes induce inflammation in an IL-18-dependent manner and that inflammasome-dependent IL-18 and pyroptosis restrict Brucella infection.

KEYWORDS:

Brucella; arthritis; caspase-1; caspase-11

PMID:
29941463
PMCID:
PMC6105886
DOI:
10.1128/IAI.00361-18
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center