In addition to causing neurodegeneration, the human mutant protein huntingtin also damages the immune system
Our Drosophila results help to understand the effects of innate immunity impairment on Huntington's disease progression.
Figure: Ectopic expression of mHTT (Q96) decreased number of circulating and sessile hemocytes in mHTT-expressing larvae.
Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by an expansion of CAG trinucleotide in the Huntingtin (htt) gene. Mutant HTT protein (mHTT) contains an expanded polyglutamine tract which causes cytotoxicity and leads to neurodegeneration. While most of described HD symptoms are related to neuronal dysfunction, emerging evidence indicates that the expression of mHTT in other tissues also contributes to the pathogenesis of HD. We used transgenic Drosophila expressing mutant HTT protein specifically in the hemocytes to examine its effects on fly viability, hemocyte numbers, and sensitivity to infection. We found that expressing mHTT in the hemocytes does not directly cause a lethal effect, although it reduces the number of circulating hemocytes and affects ATP synthesis in these cells. We also observed the induction of antimicrobial peptides and impairment of the immune response against different pathogens in mHTT-expressing Drosophila. Our findings provide an insight into the effect of innate immunity impairment on HD progression.
