Inflammasome activation by Gram-positive bacteria: Mechanisms of activation and regulation

Abstract

The inflammasomes are intracellular multimeric protein complexes consisting of an innate immune sensor, the adapter protein ASC and the inflammatory caspases-1 and/or -11 and are important for the host defense against pathogens. Activaton of the receptor leads to formation of the inflammasomes and subsequent processing and activation of caspase-1 that cleaves the proinflammatory cytokines IL-1β and IL-18. Active caspase-1, and in some instances caspase-11, cleaves gasdermin D that translocates to the cell membrane where it forms pores resulting in the cell death program called pyroptosis. Inflammasomes can detect a range of microbial ligands through direct interaction or indirectly through diverse cellular processes including changes in ion fluxes, production of reactive oxygen species and disruption of various host cell functions. In this review, we will focus on the NLRP3, NLRP6, NLRC4 and AIM2 inflammasomes and how they are activated and regulated during infections with Gram-positive bacteria, including Staphylococcus spp., Streptococcus spp. and Listeria monocytogenes.

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“…The neutrophil recruitment pathway is initiated when lipopolysaccharide (LPS) from Gram-negative bacteria or lipoteichoic acid (LPA) from Gram-positive bacteria is visible to macrophages and epithelial cells. Both of these substances cause the production of TNF and IL1B [75]. Therefore, it is assumed that an infectious agent caused the great mainstream of the eweimpacted cases of inflammatory reproductive disease in our investigation.…”

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“… 2018 ; Downs et al. 2020 ; Keestra-Gounder and Nagao 2023 ) as summarized in Figure 3 . Dysregulated inflammasome activation can cause tissue damage in host due to an exaggerated innate immune response.…”

“…Dysregulated inflammasome activation can cause tissue damage in host due to an exaggerated innate immune response. Gram-positive pathogens employ a variety of virulence strategies to elude detection by inflammasomes in host cells and prevent the induction of pyroptosis (Keestra-Gounder and Nagao 2023 ).…”

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“…ASC structurally consist of PYD and CARD, whereas procaspase-1 has a CARD structure; therefore, it can promotes PYD and CARD homotypic interactions between sensors (NLRs or PYHIN) and procaspase-1 ( 25 ). Procaspase-1 can be recruited to complexes in two different ways: via the junction with ASC or via CARD–CARD interactions, which represents direct contact ( 26 ). All six inflammasome receptors can recruit procaspase-1 in an ASC-dependent manner, whereas NLRP1 and NLRC4 may also recruit procaspase-1 to the complex via CARD–CARD interactions ( Figure 1 ).…”