Page 56 - Veterinary Immunology, 10th Edition

turns on another transcription factor, IRF3, that activates the gene
VetBooks.ir
for IFN-β.

The proteins produced in response to TLR-ligation on sentinel
cells are known as cytokines, proteins that regulate the cells
involved in the defense of the body. These cytokines are produced

as inactive precursors and then activated by an enzyme called
caspase-1. The production of caspase-1 is triggered by a protein
complex called an inflammasome (Box 2.2). Caspases are proteases
(cysteinyl aspartate-specific proteinases). Many, such as caspase-1,

-4, -5, and -12, are activated by signals generated through TLRs.
Caspase-1 is most important because it acts on inactive precursors
to generate the active cytokines.

Box 2.2

Inflammasomes

When PAMPs and DAMPs bind to NOD-like receptors, they
initiate the assembly of large intracellular multiprotein complexes

called inflammasomes. These inflammasomes then activate two
proteolytic enzymes, caspase-1 and caspase-11. The caspase-11
triggers cell death by a process called pyroptosis. The caspase-1
acts on pro-IL-1 and pro-IL-18 to generate the active forms of these
two cytokines that are then released as cells die (see Fig. 2.9). Four

different types of inflammasome have been characterized, each
generated by different PAMPs and DAMPs, and containing
slightly different components, and thus presumably generating

different cytokines and proinflammatory molecules. In humans,
inherited defects in some inflammasome components are linked to
uncontrolled inflammation. Inflammasome-mediated responses are
important in controlling microbial infections as well as in
regulating some metabolic processes and immune responses,

especially in the intestinal mucosa. Caspase-1 deficient mice are
more susceptible to bee and snake venoms, suggesting that
inflammasomes also play a role in defense against envenomation.

Different TLRs trigger the production of different cytokine
mixtures, and different PAMPs trigger distinctly different responses

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