Page 922 - Veterinary Immunology, 10th Edition

phagolysosomes of infected macrophages. Their resistance to
VetBooks.ir intracellular destruction results from multiple mechanisms. A study

of 245 macrophage genes showed that 37% were suppressed by
Leishmania infection. Leishmania lipophosphoglycan delays

phagosome maturation, so preventing the production of nitric
oxide and inhibiting macrophage responses to cytokines. The
parasite also reduces the antigen-presenting ability of macrophages
by suppressing MHC class II expression. As a result of their

persistence, the parasites trigger chronic inflammation. Initially
characterized by granulocyte invasion, this is followed by
macrophages, lymphocytes, and NK cells that collectively form
granulomas.

Clinical leishmaniasis is directly linked to the immune response
of the infected dog. In susceptible animals, the organisms may
spread from the skin to the local lymph node, spleen, and bone
marrow within a few hours. In resistant dogs, the parasites are

restricted to the skin and draining lymph node so that the animals
either remain healthy or develop a mild, self-limited disease. These
resistant dogs mount a weak antibody response but a strong and
effective Th1 response. They may have low antibody titers, but they

produce IFN-γ in response to parasite antigens, generate type I
granulomas, mount strong delayed hypersensitivity responses, and
eventually destroy the parasites.
Resistance to Leishmania has a strong genetic component; for

example, Ibizian Hounds appear to be resistant to this parasite.
There is also an association between resistance and certain MHC
class II alleles as well as some Slc11a1 (Nramp) alleles in dogs.
Susceptible dogs, in contrast, mount a Th2 response characterized

by high antibody levels but poor cell-mediated immunity. These
differences have been attributed to the activities of IL-10 from Treg
cells. In addition, the parasite may actively suppress transcription
of the IL-12 gene, ensuring that a Th2 response predominates.

Chronic, progressive disease develops in susceptible dogs.
Parasite-laden macrophages accumulate, but the organism
continues to multiply. These macrophages spread throughout the
body, resulting in disseminated infection. Dogs develop severe
generalized nodular dermatitis, granulomatous lymphadenitis,

splenomegaly, and hepatomegaly. They show polyclonal

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