Page 870 - Veterinary Immunology, 10th Edition

Immunodeficient or immunosuppressed animals are especially
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susceptible to fungal diseases.

Fungal PAMPs acting either through the toll- or NOD-like
receptors or through cell-surface C-type lectins such as the dectins,
mannose-binding lectins, and scavenger receptors such as DC-SIGN

(CD209, Chapter 2) play a key role in early innate defenses. Thus
Dectin-1 (CD369) binds to fungal β-glucans and triggers IL-22 and
IL-23 synthesis. Both contribute to antiaspergillus resistance. IL-23
activates Th17 cells. The IL-17 produced by these cells then

activates both neutrophils and endothelial cells and promotes acute
inflammation. Dectin-3 associates with dectin-1, while Dectin-2 and
-3 form a heterodimeric PRR on macrophages that can recognize α-
mannans in Candida hyphae. DC-SIGN binds mannose. It is of

interest to note that culturing T cells and monocytes in the presence
of Candida hyphae promotes the generation of Th17 cells. In
contrast, culture in the presence of the Candida yeast form promotes
production of IL-12 and a Th1 response. Because of their size,

neutrophils cannot totally ingest invading fungi. Nevertheless, by
releasing enzymes and oxidants into the tissue fluid, neutrophils
may severely damage fungal hyphae. Small fungal fragments or
spores may be ingested and destroyed by macrophages or by NK

cells.
Once established, fungal infections are mainly destroyed by Th1-
mediated mechanisms. Thus some species of Aspergillus are
facultative intracellular parasites, and chronic or progressive fungal

diseases are commonly associated with defects in the T cell system.
Th1 cells function in fungal infections by activating macrophages
and by promoting epidermal growth and keratinization. Some T
and NK cells can exert a direct cytotoxic effect on yeasts such as

Cryptococcus neoformans and Candida albicans. It is not uncommon
for recovered animals to develop a type IV hypersensitivity to
fungal antigens. The critical importance of adaptive immunity to
fungi is seen in the way that fungal infections, such as those caused
by Pneumocystis, develop in immunosuppressed animals such as

dogs with canine distemper. Although defense against Pneumocystis
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is critically dependent upon CD4 T cell function, it is also
dependent on Th17 cells. Depletion of IL-17 or IL-23 increases the

severity of Pneumocystis pneumonia.

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