Apoptosis

, 14:522 | Cite as

Inflammasomes in infection and inflammation

  • Christian R. McIntire
  • Garabet Yeretssian
  • Maya Saleh
Cell Death and Disease

Abstract

Two of the main challenges that multicellular organisms faced during evolution were to cope with invading microorganisms and eliminate and replace dying cells. Our innate immune system evolved to handle both tasks. Key aspects of innate immunity are the detection of invaders or tissue injury and the activation of inflammation that alarms the system through the action of cytokine and chemokine cascades. While inflammation is essential for host resistance to infections, it is detrimental when produced chronically or in excess and is linked to various diseases, most notably auto-immune diseases, auto-inflammatory disorders, cancer and septic shock. Essential regulators of inflammation are enzymes termed “the inflammatory caspases”. They are activated by cellular sensors of danger signals, the inflammasomes, and subsequently convert pro-inflammatory cytokines into their mature active forms. In addition, they regulate non-conventional protein secretion of alarmins and cytokines, glycolysis and lipid biogenesis, and the execution of an inflammatory form of cell death termed “pyroptosis”. By acting as key regulators of inflammation, energy metabolism and cell death, inflammatory caspases and inflammasomes exert profound influences on innate immunity and infectious and non-infectious inflammatory diseases.

Keywords

Inflammasome Infection Inflammation Caspases Cell death 

Abbreviations

ICE

Interleukin-1β Converting Enzyme

IL-1

Interleukin-1

Asp

Aspartic acid

Ala

Alanine

Cys

Cysteine

His

Histidine

Gly

Glycine

Ser

Serine

Arg

Arginine

Glu

Glutamic acid

IGIF

Interferon-γ-inducing factor

ST2

Interleukin 1 receptor-like 1

TH1

Type 1 helper T cells

TH2

Type 2 helper T cells

TIM

Triose-phosphate isomerase

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

SREBP

Sterol regulatory element binding protein

iTRAQ

Isobaric tag for relative and absolute quantitation

FGF2

Fibroblast growth factor 2

Bid

BH3-interacting domain death agonist

AIP-1/WDR-1

Atrophin-interacting-protein 1/WD repeat domain 1

LD

Lethal dose

SIRS

Systemic inflammatory response syndrome

LPS

Lipopolysaccaride

TNFα

Tumor necrosis factor α

SAP

Severe acute pancreatitis

DSS

Dextran sodium sulfate

ARF

Acute renal failure

CTCL

Cutaneous T-cell lymphoma

VCAM-1

Vascular cell adhesion molecule-1

MS

Multiple sclerosis

EAE

Autoimmune encephalomyelitis

TLR

Toll-like receptor

NLR

Nod-like receptor

PAMP

Pathogen-associated molecular pattern

Nod

Nucleotide binding and oligomerization domain

NALP

NACHT domain- leucine-rich repeat-, and PYD-containing protein

ASC

Apoptosis-associated speck-like protein containing a CARD

Cardinal

CARD inhibitor of NF-kB-activating ligands

LRR

Leucine-rich repeat

CARD

Caspase recruitment domain

IPAF

ICE protease-activating factor

BIR

Baculovirus IAP Repeat

NAIP

Neuronal apoptosis inhibitory protein

PYD

Pyrin domain

NBS

Nucleotide binding site

DF

Death-fold

CIITA

Class II trans-activator

LCV

Legionella containing vacuole

Icm/Dot

Intracellular multiplication/defective organelle trafficking

Lgn

Legionella

IFN

Interferon

SipB

Salmonella invasion protein B

TTSS

Type III secretion system

IpaB

Invasin B

DAMP

Danger-associated molecular pattern

ATP

Adenosine triphosphate

iPLA2

Ca2+-independent phospholipase A2

MSU

Monosodium urate

CPPD

Calcium pyrophosphate dihydrate

ROS

Reactive oxygen species

NADPH

Nicotinamide adenine dinucleotide phosphate-oxidase

P22phox

Protein 22 phagocyte and oxidase

OVA

Ovalbumin

MDP

Muramyl dipeptide

HSP90

Heat shock protein 90

NF-κB

Nuclear factor-kappa B

COP

CARD-only protein

INCA

Inhibitory CARD

RIP2

Receptor-interacting protein 2

FMF

Familial Mediterranean fever

vPYD

Viral PYD

Bcl-2

B-cell lymphoma 2

Bcl-XL

Basal cell lymphoma-extra large

IKKβ

I kappa B kinase β

LOF

Loss of function

GOF

Gain of function

BLS-II

Type II bare lymphocyte syndrome

SCID

Severe combined immunodeficiency

MHC-II

Major histocompatibility complex class II

FCU

Familial cold urticaria

MWS

Muckle–Wells syndrome

NOMID

Neonatal-onset mutli-system inflammatory disease

CIAS1

Cold-induced auto-inflammatory syndrome 1

CD

Crohn’s disease

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Christian R. McIntire
    • 1
  • Garabet Yeretssian
    • 2
  • Maya Saleh
    • 1
    • 2
  1. 1.Department of BiochemistryMcGill UniversityMontrealCanada
  2. 2.Department of Medicine, Division of Critical Care, and Centre for the Study of Host ResistanceMcGill UniversityMontrealCanada

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