Engineering bacterial nanosyringes for regional immune recalibration at the oral barrier

Abstract This article outlines a conceptual and translational framework for adapting engineered bacterial nanosyringes to regional immune recalibration at the oral barrier. The oral cavity is a spatially organized barrier tissue in which epithelial, stromal and immune compartments continuously negotiate microbial exposure, mechanical injury and wound repair. Many oral inflammatory disorders therefore reflect not only microbial imbalance, but also failure of regional immune calibration. Here we propose engineered bacterial nanosyringes, particularly Photorhabdus virulence cassette (PVC)-based extracellular contractile injection systems, as a conceptual framework for cell-targeted immune recalibration at the oral barrier. Rather than presenting these systems as ready-to-use oral therapeutics, we define oral-barrier-specific design requirements, including local retention, cargo compatibility, repeated-dose immunogenicity testing, preservation of host defence and spatially resolved efficacy readouts. We further discuss illustrative cargo modules for transient inflammatory restraint or epithelial repair, while emphasizing that durable recalibration would need to arise from interruption of self-amplifying pathological circuits rather than persistent cargo activity. This framework provides a testable roadmap for adapting bacterial nanosyringe delivery to oral inflammatory disease.