title: Neisseria meningitidis subverts the polarized organization and intracellular trafficking of host cells to cross the epithelial barrier.
abstract: Translocation of the nasopharyngeal barrier by Neisseria meningitidis occurs via an intracellular microtubule-dependent pathway and represents a crucial step in its pathogenesis. Despite this fact, the interaction of invasive meningococci with host subcellular compartments and the resulting impact on their organization and function have not been investigated. The influence of serogroup B strain MC58 on host cell polarity and intracellular trafficking system was assessed by confocal microscopy visualization of different plasma membrane-associated components (such as E-cadherin, ZO-1 and transferrin receptor) and evaluation of the transferrin uptake and recycling in infected Calu-3 monolayers. Additionally, the association of N. meningitidis with different endosomal compartments was evaluated through the concomitant staining of bacteria and markers specific for Rab11, Rab22a, Rab25 and Rab3 followed by confocal microscopy imaging. Subversion of the host cell architecture and intracellular trafficking system, denoted by mis-targeting of cell plasma membrane components and perturbations of transferrin transport, was shown to occur in response to N. meningitidis infection. Notably, the appearance of all of these events seems to positively correlate with the efficiency of N. meningitidis to cross the epithelial barrier. Our data reveal for the first time that N. meningitidis is able to modulate the host cell architecture and function, which might serve as a strategy of this pathogen for overcoming the nasopharyngeal barrier without affecting the monolayer integrity.
authors: Department of Microbial Molecular Biology, Novartis Vaccines and Diagnostics (a GSK company), Siena, Italy.|Biomimetic Microsystems platform, Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, 02115, USA.
authors: Riccardo
authors: R
authors: Barrile
authors: Department of Microbial Molecular Biology, Novartis Vaccines and Diagnostics (a GSK company), Siena, Italy.
authors: Magdalena
authors: M
authors: Kasendra
authors: Department of Microbial Molecular Biology, Novartis Vaccines and Diagnostics (a GSK company), Siena, Italy.
authors: Silvia
authors: S
authors: Rossi-Paccani
authors: Department of Microbial Molecular Biology, Novartis Vaccines and Diagnostics (a GSK company), Siena, Italy.|Department of Biology, University of Naples 'Federico II', Napoli, Italy.
authors: Marcello
authors: M
authors: Merola
authors: Department of Microbial Molecular Biology, Novartis Vaccines and Diagnostics (a GSK company), Siena, Italy.
authors: Mariagrazia
authors: M
authors: Pizza
authors: Department of Life Sciences, University of Siena, Siena, Italy.
authors: Cosima
authors: C
authors: Baldari
authors: Department of Microbial Molecular Biology, Novartis Vaccines and Diagnostics (a GSK company), Siena, Italy.
authors: Marco
authors: M
authors: Soriani
authors: Department of Microbial Molecular Biology, Novartis Vaccines and Diagnostics (a GSK company), Siena, Italy.
authors: Beatrice
authors: B
authors: Aricò
mesh_terms: D002460:Cell Line; D016764:Cell Polarity; D004847:Epithelial Cells / Q000382:microbiology* / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D018613:Microscopy, Confocal; D038541:Neisseria meningitidis, Serogroup B / Q000502:physiology*; D057900:Transcytosis