J Korean Med Sci.  2013 Oct;28(10):1415-1423. 10.3346/jkms.2013.28.10.1415.

NLRP3 Inflammasome and Host Protection against Bacterial Infection

• Kim JJ
• Jo EK

• KMID: 1777675
• DOI: http://doi.org/10.3346/jkms.2013.28.10.1415

Abstract

The inflammasome is a multi-protein complex that induces maturation of inflammatory cytokines interleukin (IL)-1beta and IL-18 through activation of caspase-1. Several nucleotide binding oligomerization domain-like receptor family members, including NLRP3, recognize unique microbial and danger components and play a central role in inflammasome activation. The NLRP3 inflammasome is critical for maintenance of homeostasis against pathogenic infections. However, inflammasome activation acts as a double-edged sword for various bacterial infections. When the IL-1 family of cytokines is secreted excessively, they cause tissue damage and extensive inflammatory responses that are potentially hazardous for the host. Emerging evidence has shown that diverse bacterial pathogens or their components negatively regulate inflammasome activation to escape the immune response. In this review, we discuss the current knowledge of the roles and regulation of the NLRP3 inflammasome during bacterial infections. Activation and regulation of the NLRP3 inflammasome should be tightly controlled to prevent virulence and pathology during infections. Understanding the roles and regulatory mechanisms of the NLRP3 inflammasome is essential for developing potential treatment approaches against pathogenic infections.

Keyword

NLRP3 Protein, Human; Bacteria; Infection; Inflammation; Host Defense; Pathology

MeSH Terms

Bacterial Infections/immunology/metabolism/pathology/prevention & control
Carrier Proteins/*metabolism
Caspase 1/metabolism
Humans
Inflammasomes/immunology/*metabolism
Interleukin-1beta/metabolism
Signal Transduction
Carrier Proteins
Caspase 1
Inflammasomes
Interleukin-1beta

Figure

• 

  Fig. 1 Model of NLRP3 inflammasome activation. Activation of caspase-1 by the NLRP3 inflammasome depends a multi-signal process. Signal 1 occurs when IL-1R, TNF or a TLR ligand binds its cognate receptor resulting in the translocation of NF-κB into the nucleus where expression of Nlrp3, pro-Il1β, and Il-18 are induced. Signal 2 involves the assembly of NLRP3 inflammasome complex resulting in the recruitment of adaptor molecule ASC and pro-caspase-1, to induce processing and secretion of cytokines IL-1β and IL-18. So far, several pathways for NLRP3 inflammasome activation have been identified in bacterial infection. They include phagocytosis of certain pathogenic microbes leading to rupture of lysosomes, stimulation of P2X7R, and its opening of the pannexin-1 pore to increase potassium efflux and mitochondrial ROS. Recent studies have identified the new players, GBP5, MAVS, or VDAC, in NLRP3 inflammasome activation. In addition, microtubule-driven spatial arrangement of mitochondria was suggested to promote activation of the NLRP3 inflammasome. Nevertheless, the complete molecular mechanisms how NLRP3 inflammasome activation occurs have not been fully understood.

• 

  Fig. 2 Microbial activation of the NLRP3 inflammasomes. Pathogenic microorganisms activate the NLRP3 inflammasomes through multiple agonists and pathways. Various bacteria or their products can activate NLRP3 inflammasome activation through different mechanisms. The detailed information of NLRP3 activation or modulation by bacteria and/or their factors is described in the text.

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