Page 63 - Veterinary Immunology, 10th Edition

neutrophils release PGRP-S when exposed to bacteria. Thus PGRP-
VetBooks.ir S probably plays a significant role in the resistance of cattle to

bacterial infections.

Bacterial DNA

Bacterial deoxyribonucleic acid (DNA) can stimulate innate
immunity because it is structurally different from eukaryotic DNA.
Much of it consists of the dinucleotide, unmethylated cytosine-

guanosine (CpG). (The cytosine in eukaryotic DNA is normally
methylated, but not in prokaryotes such as bacteria.) Unmethylated
CpG dinucleotides bind and activate TLR9. Bacterial DNA also
contains deoxyguanosine (dG) nucleotides. These dG nucleotides
form molecular structures that differ from the usual DNA double

helix. They also bind to TLR9 and trigger production of cytokines
such as TNF-α, IL-6, and IL-12.

Viral Nucleic Acids

Viruses are simple structures, usually consisting of a nucleic acid
core surrounded by a layer of proteins, the capsid, and possibly a
lipid envelope (see Fig. 9.2). Viruses have few characteristic
molecular signatures. However, their nucleic acids are structurally

different from those in animals so they also bind to intracellular
PRRs. TLR9 binds DNA from viruses and intracellular bacteria,
whereas TLR7 and TLR8 bind ssRNA from viruses. TLR3, in
contrast, mainly binds viral dsRNA, but it can also recognize some

ssRNA and some dsDNA viruses. Intracellular RLRs also bind and
respond to viral dsRNA. TLR7 and TLR9 activate the MyD88-
mediated signaling pathways and trigger production of
inflammatory cytokines and type I IFNs. TLR3 uses another

signaling molecule, the TIR-domain-containing adaptor protein
inducing IFN-β (TRIF). The TRIF pathway activates the
transcription factor IRF3 that then activates the genes for
inflammatory cytokines and IFN-β.

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