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Inflammasomes in infection and inflammation

  • Cell Death and Disease
  • Published:
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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.

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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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Authors and Affiliations

  1. Department of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada

    Christian R. McIntire & Maya Saleh

  2. Department of Medicine, Division of Critical Care, and Centre for the Study of Host Resistance, McGill University, Montreal, QC, H3G 0B1, Canada

    Garabet Yeretssian & Maya Saleh

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  1. Christian R. McIntire
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  2. Garabet Yeretssian
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  3. Maya Saleh
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Correspondence to Maya Saleh.

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Christian R. McIntire and Garabet Yeretssian have contributed equally to this review.

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McIntire, C.R., Yeretssian, G. & Saleh, M. Inflammasomes in infection and inflammation. Apoptosis 14, 522–535 (2009). https://doi.org/10.1007/s10495-009-0312-3

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