August 24, 2017

New Findings on the Pathogenesis of Canine Demodicosis

A recent study has provided an answer to the longstanding question of the pathogenesis of canine demodicosis.
By JoAnna Pendergrass, DVM
Canine demodicosis is a common veterinary dermatologic disease typically treated with parasiticides. However, it has often been difficult to manage and prevent because of its unknown pathogenesis. Previous studies have proposed immunosuppressive activities of canine demodicosis, including downregulation or apoptosis of T helper (Th) cells.

The nervous system helps modulate immune system function and inflammation. In particular, neural cholinergic pathways regulate pro- and anti-inflammatory cytokine production and release. For example, acetylcholine suppresses the release of tumor necrosis factor alpha (TNFα), a pro-inflammatory cytokine.

Interestingly, several previous studies have reported a possible association between anti-inflammatory cytokines and canine demodicosis. The exact immunologic mechanisms for the disease’s progression, though, have remained unclear.

In a study recently published in Parasitology, an Indian research team determined that canine demodicosis activates cholinergic anti-inflammatory pathways to suppress inflammation, allowing Demodex canis mites to flourish on a dog’s skin. “Our study,” the researchers wrote, “demonstrates, for the first time, the association of cholinergic activation with demodicosis in dogs.”

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Examination
Thirty dogs aged 1 to 3 years with demodicosis were examined at the Teaching Veterinary Clinical Complex in India. The researchers performed skin scrapings, hair plucks, and skin lesion impression smears. The dogs, which were free of other diseases, were grouped according to demodicosis status:
  • Group 1 – localized demodicosis (LD)
  • Group 2 – generalized demodicosis (GD) without pyoderma
  • Group 3 – GD with pyoderma
Age-matched healthy dogs were used as controls.
Blood samples were collected for several measurements:
  • Serum cholinesterase activity, as an indirect measure of acetylcholine levels
  • Pro-inflammatory TNFα and interferon gamma (IFNγ) levels
  • Anti-inflammatory interleukin-10 (IL-10) levels
Results
Cholinesterase activity was significantly higher in dogs with demodicosis than in healthy dogs, indicating acetylcholine overproduction with canine demodicosis infections. This activity was highest in dogs with GD, suggesting cholinergic pathway activation with disease progression and secondary bacterial infection.

TNFα levels were highest in dogs with GD + pyoderma, indicating an amplified immune response with secondary bacterial infection. Notably, TNFα levels in dogs with LD and GD without pyoderma were significantly lower than those in healthy dogs. IFNγ levels were not significantly different between groups.

IL-10 levels were significantly higher in dogs with GD than in healthy dogs and dogs with LD, and highest in dogs with GD + pyoderma. These findings illustrate a potential association between IL-10 overproduction and progression from LD to GD, the researchers believed.

Role of Th cells
Th1 cells produce IFNγ and TNFα, while Th2 cells produce IL-10. Given the study’s findings, the researchers proposed that Demodex mites ensure their survival and proliferation by enhancing Th2 cells’ production of IL-10, which could possibly suppress Th1 cytokine production.

Looking Forward
The cholinergic pathway’s pathogenic role in canine demodicosis aligns with this pathway’s previously reported role in the maintenance and progression of other canine parasitic diseases, such as leishmaniasis. Looking forward, the researchers emphasized that an “understanding of the immunopathology of canine demodicosis is warranted for opening the novel and newer therapeutic windows for management of clinical manifestations in canines.”

 
Dr. Pendergrass received her Doctor of Veterinary Medicine degree from the Virginia-Maryland College of Veterinary Medicine. Following veterinary school, she completed a postdoctoral fellowship at Emory University’s Yerkes National Primate Research Center. Dr. Pendergrass is the founder and owner of JPen Communications, a medical communications company.

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