How Ehrlichia canis infection causes immune and cell stress in dogs

Abstract

Ehrlichia canis (E. canis) infection elicits a pronounced systemic inflammatory response in dogs; however, the contribution of endoplasmic reticulum (ER) stress-mediated apoptotic mechanisms to disease pathogenesis remains largely unexplored. This study aimed to elucidate the interplay between immune activation, ER stress signaling, and apoptosis in dogs naturally infected with E. canis. Thirty mixed-breed dogs aged 3-6 years were enrolled, including 20 dogs with confirmed ehrlichiosis and 10 clinically healthy controls. Molecular characterization revealed that E. canis isolates shared 100% sequence identity with previously reported Turkish and international reference strains. Infected dogs exhibited significantly elevated serum IgG and IgM concentrations compared with controls, accompanied by marked upregulation of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. Notably, all three major ER stress signaling branches were activated, as evidenced by significant upregulation of PERK, IRE1-α, ATF6, and the pro-apoptotic transcription factor CHOP. Furthermore, apoptosis-related gene expression analysis demonstrated increased Bax and caspase-12 expression together with downregulation of the anti-apoptotic gene BCL-2. Collectively, these findings demonstrate that natural E. canis infection concurrently activates ER stress signalling and ER stress-associated apoptotic pathways in parallel with a robust inflammatory response. This study provides insight into the molecular mechanisms involved in the pathogenesis of canine ehrlichiosis and identifies the ER stress-apoptosis axis as a critical contributor to disease progression.