Involvement of caspase-1 in inflammasomes activation and bacterial clearance in S. aureus-infected osteoblast-like MG-63 cells

Elma Lima Leite (1, 2) , Arthur Gautron (3) , Martine Deplanche (1) , Aurélie Nicolas (1) , Jordane Ossemond (1) , Minh-Thu Nguyen (4) , Fillipe L. R. Do Carmo (1, 2) , David Gilot (3) , Vasco Azevedo (2) , Friedrich Goetz (5) , Yves Le Loir (1) , Michael Otto (6) , Nadia Berkova (1)

1 STLO - Science et Technologie du Lait et de l'Oeuf
2 UFMG - Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil]
3 IGDR - Institut de Génétique et Développement de Rennes
4 EPI - Paul-Ehrlich-Institute - Federal Institute for Vaccines and Biomedicines
5 Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen
6 NIAID-NIH - National Institute of Allergy and Infectious Diseases [Bethesda]

Staphylococcus aureus, a versatile Gram-positive bacterium, is the main cause of bone and joint infections (BJI), which are prone to recurrence. The inflammasome is an immune signaling platform that assembles after pathogen recognition. It activates proteases, most notably caspase-1 that proteolytically matures and promotes the secretion of mature IL-1 beta and IL-18. The role of inflammasomes and caspase-1 in the secretion of mature IL-1 beta and in the defence of S. aureus-infected osteoblasts has not yet been fully investigated. We show here that S. aureus-infected osteoblast-like MG-63 but not caspase-1 knock-out CASP1( -/-)MG-63 cells, which were generated using CRISPR-Cas9 technology, activate the inflammasome as monitored by the release of mature IL-1 beta. The effect was strain-dependent. The use of S. aureus deletion and complemented phenole soluble modulins (PSMs) mutants demonstrated a key role of PSMs in inflammasomes-related IL-1 beta production. Furthermore, we found that the lack of caspase-1 in CASP1( -/-)MG-63 cells impairs their defense functions, as bacterial clearance was drastically decreased in CASP1( -/-) MG-63 compared to wild-type cells. Our results demonstrate that osteoblast-like MG-63 cells play an important role in the immune response against S. aureus infection through inflammasomes activation and establish a crucial role of caspase-1 in bacterial clearance.

Keywords: CRISPR-Cas9 gene editing; inflammasomes; bacterial clearance; caspase-1; Staphylococcus aureus

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Microbiology and Parasitology

Elma Lima Leite, Arthur Gautron, Martine Deplanche, Aurélie Nicolas, Jordane Ossemond, et al.. Involvement of caspase-1 in inflammasomes activation and bacterial clearance in S. aureus-infected osteoblast-like MG-63 cells. Cellular Microbiology, 2020, 22 (8), pp.e13204. ⟨10.1111/cmi.13204⟩. ⟨hal-02565096⟩