Bystander monocytic cells drive infection-independent NLRP3 inflammasome response to SARS-CoV-2
Inflammasome activation is associated with severe COVID-19. The impact of inflammasome activation on viral replication and mechanistic details of this activation are not clarified. This study advances our understanding of the role of inflammasome activation in macrophages by identifying TLR2, NLRP3, ASC, and caspase-1 as dependent factors in this activation. Further, it highlights that SARS-CoV-2 inflammasome activation is not a feature of nasal epithelial cells but rather activation of bystander macrophages in the airway. Finally, we demonstrate that two pro inflammatory cytokines produced by inflammasome activation, IL-18 and IL-1β, do not restrict viral replication and are potential targets to ameliorate pathological inflammation in severe COVID-19.
Authors
- Petros C. Karakousis (ORCID: https://orcid.org/0000-0003-1338-9206)
- Guido Massaccesi (ORCID: https://orcid.org/0000-0002-4528-0937)
- Eduardo Anaya
- Alvaro A. Ordoñez (ORCID: https://orcid.org/0000-0002-8571-0655)
- Leon L. Hsieh (ORCID: https://orcid.org/0000-0002-6920-7718)
- Franco R. D’Alessio (ORCID: https://orcid.org/0000-0002-3728-0064)
- Alexis Figueroa (ORCID: https://orcid.org/0000-0002-6549-3489)
- Victor R. DeFilippis
- Monika M. Looney (ORCID: https://orcid.org/0000-0002-3295-5528)
- Andrew Pekosz (ORCID: https://orcid.org/0000-0003-3248-1761)
- Andrew H. Karaba (ORCID: https://orcid.org/0000-0003-2785-317X)
- Georgia Stavrakis
- Andrea L. Cox (ORCID: https://orcid.org/0000-0002-9331-2462)
Institutions
- Johns Hopkins University (US)
- Oregon Health & Science University (US)
- Johns Hopkins Medicine (US)
Publication Details
- Journal
- mBio
- Published
- 2024-09-06
- DOI
- https://doi.org/10.1128/mbio.00810-24
- Citations
- 5
- Primary Topic
- Inflammasome and immune disorders
- Type
- article
- Field-Weighted Citation Impact
- 1.17
Funders
- Bill and Melinda Gates Foundation
- Johns Hopkins University
- National Institutes of Health
- Health Resources and Services Administration
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases