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Pannexin-1-Mediated Intracellular Delivery of Muramyl Dipeptide Induces Caspase-1 Activation via Cryopyrin/NLRP3 Independently of Nod2

Marina-García, Noemí, Franchi, Luigi, Kim, Yun-Gi, Miller, Douglas, McDonald, Christine, Boons, Geert-Jan, Núñez, Gabriel·2008·The Journal of Immunology

Abstract

Muramyl dipeptide (MDP), the microbial activator of nucleotide-binding oligomerization domain 2 (Nod2), induces NF-κB and MAPK activation, leading to the production of multiple anti-bacterial and proinflammatory molecules. In addition, MDP has been implicated in IL-1β secretion through the regulation of caspase-1. However, the mechanisms that mediate caspase-1 activation and IL-1β secretion in response to MDP stimulation remain poorly understood. We show here that fluorescent MDP molecules are internalized in primary macrophages and accumulate in granular structures that colocalize with markers of acidified endosomal compartments. The uptake of MDP was Nod2-independent. Upon ATP stimulation, labeled MDP was rapidly released from acidified vesicles into the cytosol, a process that required functional pannexin-1. Caspase-1 activation induced by MDP and ATP required pannexin-1 and Cryopyrin but was independent of Nod2. Conversely, induction of pro-IL-1β mRNA by MDP stimulation was abolished in Nod2-deficient macrophages but unimpaired in macrophages lacking Cryopyrin. These studies demonstrate a Nod2-independent mechanism mediated through pore-forming pannexin-1 that is required for intracellular delivery of MDP to the cytosol and caspase-1 activation. Furthermore, the work provides evidence for distinct roles of Nod2 and Cryopyrin in the regulation of MDP-induced caspase-1 activation and IL-1β secretion.

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Metadata

Authors
Marina-García, N., Franchi, L., Kim, Y.-G., Miller, D., McDonald, C., Boons, G.-J., & Núñez, G.
Venue
The Journal of Immunology
Published
2008-03
Volume
180
Issue
6
Pages
4050-4057
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W1585170322
Cited by
169
References
10
FWCI
9.43
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Pannexin-1-Mediated Intracellular Delivery of Muramyl Dipeptide Induces Caspase-1 Activation via Cryopyrin/NLRP3 Independently of Nod2. https://app.cochat.ai/papers/10.4049/jimmunol.180.6.4050
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Marina-García, N., Franchi, L., Kim, Y.-G., Miller, D., McDonald, C., Boons, G.-J., & Núñez, G. (2008). Pannexin-1-Mediated Intracellular Delivery of Muramyl Dipeptide Induces Caspase-1 Activation via Cryopyrin/NLRP3 Independently of Nod2. The Journal of Immunology. https://doi.org/10.4049/jimmunol.180.6.4050

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.