Internalization of Lactobacillus crispatus Through Caveolin-1-Mediated Endocytosis Boosts Cellular Uptake but Blocks the Transcellular Passage of Neisseria meningitidis

<i>Neisseria meningitidis</i> is a human-specific pathogen that colonizes the nasopharyngeal epithelium, which is populated by a dynamic microbiota that includes <i>Lactobacillus</i> species. Currently, little is known about the interaction between commensal lactobacilli and pathogenic <i>Neisseria</i>, emphasizing a need for deeper studies into the molecular interactions between the two bacteria species. This, in turn, could add clinical and therapeutic value to existing treatments against an <i>N. meningitidis</i> infection. In this work, we explored how lactobacilli affect the interplay between <i>N. meningitidis</i> and host cells. We report that <i>Lactobacillus crispatus</i>, but not other tested <i>Lactobacillus</i> species, efficiently enters pharyngeal cells via caveolin-mediated lipid raft endocytosis and simultaneously enhances the uptake of <i>N. meningitidis</i>, as well as uptake of other pathogenic and non-pathogenic microbes. After promoting internalization, <i>L. crispatus</i> then prevented <i>N. meningitidis</i> from being released and transcytozed from a confluent cell layer on microporous transwell membranes. Infected cells increased the level of acidic vacuoles and pathogen clearance over time, while lactobacilli survived inside the cells. Taken together, the data suggest a possible route through which the cellular uptake of lactobacilli can increase the uptake of pathogens for destruction.