Trisomy 21 (Down Syndrome, DS) is the most common chromosomal anomaly. Although 
DS is mostly perceived as affecting cognitive abilities and cardiac health, 
individuals with DS also exhibit dysregulated immune functions. Levels of 
pro-inflammatory cytokines are increased, but intrinsic alterations of innate 
immunity are understudied in DS. Furthermore, elevated Reactive Oxygen Species 
(ROS) are well documented in individuals with DS, further exacerbating 
inflammatory processes. Chronic inflammation and oxidative stress are often 
precursors of subsequent tissue destruction and pathologies, which affect a 
majority of persons with DS. Together with ROS, the second messenger ion Ca2+ 
plays a central role in immune regulation. TRPM2 (Transient Receptor Potential 
Melastatin 2) is a Ca2+-permeable ion channel that is activated under conditions 
of oxidative stress. The Trpm2 gene is located on human Chromosome 21 (Hsa21). 
TRPM2 is strongly represented in innate immune cells, and numerous studies have 
documented its role in modulating inflammation. We have previously found that as 
a result of suboptimal cytokine production, TRPM2-/- mice are highly susceptible 
to the bacterial pathogen Listeria monocytogenes (Lm). We therefore used Lm 
infection to trigger and characterize immune responsiveness in the DS mouse 
model Dp10(yey), and to investigate the potential contribution of TRPM2. In 
comparison to wildtype (WT), Dp10(yey) mice show an increased resistance against 
Lm infection and higher IFNγ serum concentrations. Using a gene elimination 
approach, we show that these effects correlate with Trpm2 gene copy number, 
supporting the notion that Trpm2 might promote hyperinflammation in DS.