Key role of caspase-1 in bacterial clearance during S. aureus infection of osteoblasts-like cells. - Université de Rennes Accéder directement au contenu
Poster De Conférence Année : 2021

Key role of caspase-1 in bacterial clearance during S. aureus infection of osteoblasts-like cells.

Résumé

Staphylococcus aureus (S. aureus), a versatile Gram-positive bacterium, is the main cause of bone and joint infections, 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-1β and IL-18. The role of inflammasomes and caspase-1 in the secretion of mature IL-1β and in the defence of S. aureus-infected non-professional phagocytes, human osteoblast-like MG-63 cells, has not yet been fully investigated. To investigate the role of inflammasomes in S. aureus-infected MG-63 cells, the establishement of CASP1–/–MG-63 cell line was carried out using the CRISPR-Cas9 gene editing system. We and others showed that S. aureus can be internalized and survive within professional phagocytes, such as macrophages as well as within non phagocytic epithelial cells or osteoblasts. To study the capacity of intracellular S. aureus to induce inflammasomes formation in MG-63 cells, we confirmed the presence of intracellular bacteria using transmission electron microscopy We show here that S. aureus-infected MG-63 cells but not caspase-1 knock-out CASP1–/–MG-63 cells activate the inflammasome as monitored by the release of mature IL-1β. The effect was strain-dependent. The quorum-sensing system in S. aureus known as the accessory gene regulator (Agr) regulates the expression of many virulence factors including the expression of most S. aureus toxin genes. Of note, the expression of PSMs encoding genes (PSMα 1 to 4, PSMβ 1 and 2, and δ-toxin sometimes called PSMƔ) is tightly controlled by the Agr system. The use of S. aureus LAC (USA300) wild-type strain, its deletion and complemented phenole soluble modulins (PSMs) mutants demonstrated that PSM toxins are involved in inflammasomes-related IL-1β production by infected MG-63 cells. 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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hal-03356389 , version 1 (28-09-2021)

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  • HAL Id : hal-03356389 , version 1

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Elma Lima Leite, Arthur Gautron, Aurélie Nicolas, Jordane Ossemond, Fillipe L R Do Carmo, et al.. Key role of caspase-1 in bacterial clearance during S. aureus infection of osteoblasts-like cells.. SFM Microbes 2021, Sep 2021, Nantes, France. , 2021. ⟨hal-03356389⟩
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