Involvement of caspase-1 in inflammasomes activation and bacterial clearance in S. aureus-infected osteoblast-like MG-63 cells - Université de Rennes Access content directly
Journal Articles Cellular Microbiology Year : 2020

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

Jordane Ossemond
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Yves Le Loir

Abstract

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.
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Dates and versions

hal-02565096 , version 1 (14-05-2020)

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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⟩
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