Page 58 - Veterinary Immunology, 10th Edition

common in German Shepherd dogs. Genetic analysis of a large
VetBooks.ir number of affected dogs showed that several single-nucleotide

polymorphisms (SNPs) in the TLR4 and TLR5 genes were
associated with the occurrence of this disease. It is likely that in

German Shepherd dogs, mutations in their TLR4 and TLR5 genes
reduced their ability to defend against intestinal bacterial invasion.
This predisposes to enteric infections, as shown by diarrhea and
vomiting.

Kathrani A, House A, Catchpole B, et al: Polymorphisms in the TLR4 and TLR5 gene are
significantly associated with inflammatory bowel disease in German Shepherd dogs, PloS
One 5:e15740, 2010.

RIG-1-Like Receptors

Retinoic acid inducible gene (RIG)-like receptors (RLRs) are another

family of PRRs expressed within cells. They detect viral double-
stranded (ds) RNA molecules. Because dsRNA molecules do not
occur in uninfected cells, their detection by RLRs activates caspases

and triggers the production of type I interferons.

NOD-Like Receptors

Nucleotide-binding oligomerization domain (NOD)-like receptors
(NLRs) are a family of PRRs that detect intracellular PAMPs (Table

2.2). Although TLRs and NLRs differ in their location and function,
they both react to microbial PAMPs and trigger innate responses to
invaders. NOD1 binds bacterial peptidoglycans, whereas NOD2

binds muramyl dipeptide and serves as a general sensor of
intracellular bacteria. Binding to either NLR activates the NF-κB
pathway and triggers the production of proinflammatory cytokines
(Fig. 2.6). NOD2 binding also triggers the production of the
antimicrobial proteins called defensins (Chapter 3). NOD3 binds

diverse ligands including many viral nucleic acids and inorganic
matter such as silica, asbestos, and alum.

TABLE 2.2
Other Mammalian Pattern-Recognition Receptors

Receptor Location Ligand Source of Ligand

58