CD8+ T cell priming in oral mucosa-draining lymph nodes supports systemic immunity

The gastrointestinal (GI) tract constitutes an essential barrier against ingested pathogens. While immune reactions are well-studied in the lower GI tract, it remains unclear how adaptive immune responses are initiated during microbial challenge of the oral mucosa, the primary site of pathogen encounter in the upper GI tract. Here, we identify mandibular lymph nodes (mandLN) as sentinel lymphoid organs that collect orally administered Listeria monocytogenes (Lm), leading to local CD8+ T cell activation. In contrast to CD8+ T effector cells (TEFF) generated in mesenteric lymph nodes, mandLN CD8+ TEFF lacked a gut-seeking phenotype but contributed to systemic host protection. Accordingly, mandLN stromal and dendritic cells expressed low levels of enzymes required for gut homing imprinting. Our findings extend the concept of regional specialization of immune responses along the length of the GI tract, with mandLN acting as oral lymph-draining counterparts of intestinal lymph-draining LN of the lower GI tract. SummaryListeria monocytogenes ingestion leads to priming of cytotoxic T cells in oral mucosa draining mandibular lymph nodes, which contribute to systemic host protection.