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Inflammasomes as polyvalent cell death platforms

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Abstract

Inflammasomes are multi-protein platforms that are organized in the cytosol to cope with pathogens and cellular stress. The pattern recognition receptors NLRP1, NLRP3, NLRC4, AIM2 and Pyrin all assemble canonical platforms for caspase-1 activation, while caspase-11-dependent inflammasomes respond to intracellular Gram-negative pathogens. Inflammasomes are chiefly known for their roles in maturation and secretion of the inflammatory cytokines interleukin-(IL)1β and IL18, but they can also induce regulated cell death. Activation of caspases 1 and 11 in myeloid cells can trigger pyroptosis, a lytic and inflammatory cell death mode. Pyroptosis has been implicated in secretion of IL1β, IL18 and intracellular alarmins. Akin to these factors, it may have beneficial roles in controlling pathogen replication, but become detrimental in the context of chronic autoinflammatory diseases. Inflammasomes are increasingly implicated in induction of additional regulated cell death modes such as pyronecrosis and apoptosis. In this review, we overview recent advances in inflammasome-associated cell death research, illustrating the polyvalent roles of these macromolecular platforms in regulated cell death signaling.

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Acknowledgments

We apologize to colleagues whose work is not cited due to space constraints. N.V.O. is a postdoctoral fellow with the Research Foundation Flanders. Work in ML’s laboratory is supported by Grants from VIB, Ghent University (BOF 01N02313, BOF 01J11113, BOF14/GOA/013), the Fund for Scientific Research-Flanders (Grants G030212 N and G011315 N), and the European Research Council (Grant 281600).

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  1. NOD-like Receptor and Inflammasome Laboratory, Inflammation Research Center, VIB, Technologiepark 927, B-9052, Zwijnaarde, Belgium

    Nathalia M. de Vasconcelos, Nina Van Opdenbosch & Mohamed Lamkanfi

  2. Department of Internal Medicine, Ghent University, B-9000, Ghent, Belgium

    Nathalia M. de Vasconcelos, Nina Van Opdenbosch & Mohamed Lamkanfi

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  1. Nathalia M. de Vasconcelos
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Correspondence to Mohamed Lamkanfi.

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de Vasconcelos, N.M., Van Opdenbosch, N. & Lamkanfi, M. Inflammasomes as polyvalent cell death platforms. Cell. Mol. Life Sci. 73, 2335–2347 (2016). https://doi.org/10.1007/s00018-016-2204-3

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