Gut immune and redox transcriptional responses to Borrelia infection in questing Ixodes ricinus

Ticks of the genus Ixodes are major vectors of pathogens of medical and veterinary importance, including the causative agents of Lyme borreliosis. While much is known about tick immune responses during feeding, the molecular mechanisms that enable pathogen persistence during the off-host period remain poorly understood. Here, we investigated the gut immune landscape of questing Ixodes ricinus females naturally infected with members of the Borrelia burgdorferi sensu lato species complex. Transcriptional profiling of gut tissues revealed sustained upregulation of the NF-κB transcription factor dorsal and redox-associated genes in Borrelia-infected individuals, whereas other selected immune signalling pathway genes and antimicrobial peptides remained unchanged. Correlation analyses further indicated that Borrelia load was positively associated with gene expression levels, while redox genes were strongly co-regulated, indicating a coordinated control of oxidative homeostasis. These findings point to a targeted immune response that supports gut homeostasis rather than triggering broad antimicrobial activity. However, the limited number of Borrelia-positive questing ticks analyzed in this study highlights the need for further investigations with larger sample sizes, multiple developmental stages, and additional infection experiments to validate and expand these findings.