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- Title
Microbial uptake in oral mucosa–draining lymph nodes leads to rapid release of cytotoxic CD8<sup>+</sup> T cells lacking a gut-homing phenotype.
- Authors
Barreto de Albuquerque, Juliana; Altenburger, Lukas M.; Abe, Jun; von Werdt, Diego; Wissmann, Stefanie; Martínez Magdaleno, Jose; Francisco, David; van Geest, Geert; Ficht, Xenia; Iannacone, Matteo; Bruggmann, Remy; Mueller, Christoph; Stein, Jens V.
- Abstract
The gastrointestinal (GI) tract constitutes an essential barrier against ingested microbes, including potential pathogens. Although 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 (OM), the primary site of microbial encounter in the upper GI tract. Here, we identify mandibular lymph nodes (mandLNs) as sentinel lymphoid organs that intercept ingested Listeria monocytogenes (Lm). Oral Lm uptake led to local activation and release of antigen-specific CD8+ T cells that constituted most of the early circulating effector T cell (TEFF) pool. MandLN-primed TEFF disseminated to lymphoid organs, lung, and OM and contributed substantially to rapid elimination of target cells. In contrast to CD8+ TEFF generated in mesenteric LN (MLN) during intragastric infection, mandLN-primed TEFF lacked a gut-seeking phenotype, which correlated with low expression of enzymes required for gut-homing imprinting by mandLN stromal and dendritic cells. Accordingly, mandLN-primed TEFF decreased Lm burden in spleen but not MLN after intestinal infection. Our findings extend the concept of regional specialization of immune responses along the length of the GI tract, with CD8+ TEFF generated in the upper GI tract displaying homing profiles that differ from those imprinted by lymphoid tissue of the lower GI tract. Organized immunity in the oral mucosa: The oral cavity is the first site of contact with foodborne pathogens, yet how adaptive immune responses to antigens in the oral mucosa are regulated is not well understood. Barreto de Albuquerque et al. modeled foodborne listeriosis using oral Listeria monocytogenes (Lm) infection in mice. Lm drained from the oral mucosa to mandibular lymph nodes (mandLNs), resulting in local CD8+ T cell activation and effector (TEFF) generation. MandLN-primed TEFF disseminated to the lung, oral mucosa, and secondary lymph nodes to mount protective effector responses, but not to the small intestine due to reduced expression of gut-homing receptors. These findings highlight that priming of CD8+ T cells in mandLN contributes to host protection and extend the concept of compartmentalized immune responses within the GI tract.
- Publication
Science Immunology, 2022, Vol 7, Issue 72, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.abf1861