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

Abstract

Neisseria meningitidis is a human-specific pathogen that colonizes the nasopharyngeal epithelium, which is populated by a dynamic microbiota that includes Lactobacillus species. Currently, little is known about the interaction between commensal lactobacilli and pathogenic Neisseria, 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 N. meningitidis infection. In this work, we explored how lactobacilli affect the interplay between N. meningitidis and host cells. We report that Lactobacillus crispatus, but not other tested Lactobacillus species, efficiently enters pharyngeal cells via caveolin-mediated lipid raft endocytosis and simultaneously enhances the uptake of N. meningitidis, as well as uptake of other pathogenic and non-pathogenic microbes. After promoting internalization, L. crispatus then prevented N. meningitidis 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.

Keywords

• <i>Lactobacillus</i>
• <i>Neisseria meningitidis</i>
• invasion
• caveolin-mediated endocytosis
• pathogenic clearance