Page 57 - Veterinary Immunology, 10th Edition

even within a single cell type. For example, TLRs that bind bacterial
VetBooks.ir PAMPs tend to trigger the production of cytokines optimized to

combat bacteria, while those that bind viral PAMPs produce
antiviral cytokines, and so forth. TLRs not only trigger innate

responses such as inflammation but also begin the process of
“turning on” the adaptive immune system. For example, DAMPs
binding to TLR4 trigger macrophages and their close relatives, the
dendritic cells, to produce cytokines that are potent stimulators of

lymphocytes (Chapter 8). The intracellular TLRs detect the presence
of viral nucleic acids. When triggered, they synthesize antiviral
cytokines, collectively called type I interferons (IFNs). These
interferons turn on antiviral pathways and “interfere” with viral

growth.
TLRs are mainly expressed on the cells most likely to encounter
invaders. These include neutrophils, macrophages, dendritic cells,
and epithelial cells, such as the enterocytes that line the intestine.

However, dendritic cells and macrophages include many different
cell types. Their TLR expression may differ between
subpopulations and depends on the degree of cellular activation.
TLRs are also expressed on bone marrow stem cells, the source of

blood leukocytes. Bacterial lipopolysaccharides binding to TLR4 on
these stem cells stimulates increased leukocyte production. An
increase in leukocyte numbers in the blood (the white cell count) is
therefore a consistent feature of bacterial diseases.

The TLRs of the major domestic species have been examined in
detail. They appear to be similar to the TLRs of humans and
rodents. They also vary in structure (they are “polymorphic”), and
these variations influence an animal's resistance to infections. Thus

some bovine TLR polymorphisms are associated with resistance to
mastitis and Johne's disease (Box 2.3).

Box 2.3

TLRs and Diarrhea in German Shepherd

Dogs

TLRs trigger the initial steps in resistance to microbial invaders. If
they are ineffective, an animal may show increased susceptibility to
infections. For example, chronic enteric disease is especially

57