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inflammasome

Friday 11 January 2008

Pattern-recognition receptors, such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs), are able through the recognition of pathogen-associated molecular patterns and danger-associated molecular patterns to sense microbe-dependent and microbe-independent danger and thereby initiate innate immune responses.

The innate immune system provides the host with an immediate and rapid defense against invading microbes. Detection of foreign invaders is mediated by a class of receptors that are known as the pattern recognition receptors, such as the family of Toll-like receptors (TLRs).

NALPs

NALPs are implicated in the activation of proinflammatory caspases (CASP1) (MIM.147678) via their involvement in multiprotein complexes called inflammasomes.

Toll-like receptors (TLRs)

In humans, ten functional TLRs have been identified and they respond to conserved pathogen-associated molecular patterns derived from bacteria, mycoplasma, fungi and viruses. TLR activation leads to direct antimicrobial activity against both intracellular and extracellular bacteria, and induces an antiviral gene program.

TLR2 activation leads to the use of vitamin D3 as a mechanism to combat Mycobacterium tuberculosis.

Pathology

In some autoinflammatory conditions, abnormalities in NLR signaling pathways and NLRs are involved in pathogenesis, as exemplified by NOD2 mutations associated with Crohn’s disease. Some other NLRs are components of the inflammasome, a caspase-1- and prointerleukin-1beta-activating complex.

The inflammasome has a central role in innate immunity. Some monogenic hereditary inflammatory diseases, such as Muckle-Wells syndrome, are associated with mutations in proteins that modulate the activity of the inflammasome, and on some multifactorial disorders, such as Type 2 diabetes and hypertension.

inflammasome

D. Systemic pathology

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