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Strategies that modulate inflammasomes—insights from host–pathogen interactions

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Abstract

The innate immune system is a dynamic and complex network for recognizing and responding to cellular insult or tissue damage after infection or injury. The primary effector mechanism of innate immunity is the generation of acute and chronic inflammatory responses through regulation of the processing and activation of proinflammatory caspases, particularly caspase 1, and cytokines, most notably IL-1β and IL-18. Inflammasomes, cytosolic multi-protein complexes that function as molecular scaffolds for caspase activation, have recently emerged as the pivotal mechanism by which host innate immune and inflammatory responses are regulated. In this review, we investigate the mechanisms by which inflammasomes are modulated, both by endogenous host systems and by microbial pathogens.

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Abbreviations

ASC:

apoptosis-associated speck-like protein containing CARD

ATP:

adenosine triphosphate

CAPS:

cryopyrin-associated periodic syndromes

CARD:

caspase activation and recruitment domain

caspase:

cysteine-aspartate proteases

COP:

CARD-only protein

DDF:

death domain fold

FCAS:

familial cold autoinflammatory syndrome

IL:

interleukin

IL-1R:

IL-1 receptor

IFN:

interferon

IPAF:

ICE-protease activating factor

IRF:

interferon response factor

LPS:

lipopolysaccharide

LRR:

leucine-rich repeat region

MDP:

muramyl dipeptides

MWS:

Muckle–Wells syndrome

NACHT:

NAIP, C2TA, HET-E, and TP1 domain

NALP:

NACHT-, LRR- and PYD-containing protein

NF-κB:

nuclear transcription factor κB

NLR:

NOD-like receptor

NOD:

nucleotide binding and oligomerization domain

NOMID:

neonatal-onset multisystem inflammatory disease

p38MAPK:

p38 mitogen-activated protein kinase

PAMP:

pathogen-associated molecular pattern

POP:

PYD-only protein

PRR:

pathogen recognition receptor

PYD:

PYRIN domain

TIR:

Toll/interleukin-1 receptor

tlpA:

TIR-like protein A

TLR:

Toll-like receptor

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Authors and Affiliations

  1. Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, 1600 SW Archer Rd.ARB Rm R4-295, P.O. Box 100332, Gainesville, FL, 32610, USA

    Masmudur M. Rahman & Grant McFadden

  2. Institute for Nutrisciences and Health, National Research Council Canada, 550 University Avenue, Charlottetown, PE, C1A4P3, Canada

    James B. Johnston

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  1. James B. Johnston
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Correspondence to Grant McFadden.

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Johnston, J.B., Rahman, M.M. & McFadden, G. Strategies that modulate inflammasomes—insights from host–pathogen interactions. Semin Immunopathol 29, 261–274 (2007). https://doi.org/10.1007/s00281-007-0080-5

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  • DOI: https://doi.org/10.1007/s00281-007-0080-5

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