Systemic modulation of toll-like receptors, cytokine polarization and inflammasome signaling in dogs with generalized demodicosis.

Generalized canine demodicosis caused by Demodex canis is a chronic parasitic dermatosis associated with immune dysregulation; however, the integrated molecular mechanisms underlying host-parasite interaction remain incompletely characterized. The present study investigated systemic innate and adaptive immune gene expression in dogs with generalized demodicosis compared with healthy controls using quantitative real-time PCR (qRT-PCR). Peripheral blood mononuclear cells (PBMCs) were isolated from 18 dogs with generalized demodicosis and six clinically healthy dogs. Relative mRNA expression of Toll-like receptors (TLR2, TLR6, TLR9), cytokines (IL4, IL5, IL10, IL13, IFNG, TGFB1), and the inflammasome-related gene NLRP3 was quantified and normalized to GAPDH. Dogs with generalized demodicosis showed significant upregulation of TLR2 (P = 0.030), TLR6 (P = 0.008), IL4 (P = 0.029), IL5 (P = 0.025), IL10 (P = 0.003), IL13 (P = 0.031), and NLRP3 (P = 0.001), genes along with significant downregulation of TLR9 (P = 0.014) and IFNG (P = 0.004) genes. TGFB1 gene expression was upregulated but not statistically significant. These findings demonstrate coordinated modulation of innate receptor signaling, Th2-skewed cytokine polarization, suppression of Th1-mediated immunity, and enhanced inflammasome priming in generalized demodicosis. The study provides integrated molecular evidence that generalized canine demodicosis represents a systemic immune dysregulation disorder rather than a purely localized parasitic overgrowth.