title: Neisseriae internalization by epithelial cells is enhanced by TLR2 stimulation.
abstract: Neisseria meningitidis (NM) is an opportunistic gram-negative human pathogen that colonizes the human nasopharyngeal epithelium. Asymptomatic carriage is common, but some meningococcal strains can invade nasopharyngeal epithelial cells and proceed to cause severe and often fatal infections. Invasion is predominantly driven by expression of bacterial virulence factors and host cell cognate receptors for bacterial recognition. Porins are among the Neisserial components involved in host cell activation and bacterial internalization processes. Similar to other virulence factors, porins present antigenic and structure variability among strains. Such sequence variability in the surface-exposed loop regions has been correlated to bacterial invasiveness and to variability in host cell responses via Toll-like receptor 2 (TLR2). Here, we examined whether TLR2 signaling by porins influences recovery of intracellular Neisseriae from epithelial cells in vitro. Our results show that TLR2 stimulation, either by the organism or exogenously, generally enhances Neisseriae internalization by epithelial cells. TLR2-driven intracellular signaling via ERK1/2, JNK and particularly NF-κB plays a role in this process. Based on these results, it is possible that expression of porin sequence variants that strongly induce TLR2 activation may be a mechanism to enhance the invasive features of pathogenic Neisseriae strains.
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, EBRC, 650 Albany Street, Boston, MA 02118, USA; Novartis Companion Diagnostics, 45 Sidney Street, Cambridge, MA 02139, USA.
authors.forename: Deana N
authors.initials: DN
authors.lastname: Toussi
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, EBRC, 650 Albany Street, Boston, MA 02118, USA.
authors.forename: Lee M
authors.initials: LM
authors.lastname: Wetzler
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, EBRC, 650 Albany Street, Boston, MA 02118, USA.
authors.forename: Xiuping
authors.initials: X
authors.lastname: Liu
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, EBRC, 650 Albany Street, Boston, MA 02118, USA; Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Jaharis 501b, 150 Harrison Avenue, Boston, MA 02111, USA. Electronic address: Paola.massari@tufts.edu.
authors.forename: Paola
authors.initials: P
authors.lastname: Massari
mesh_terms: D002478:Cells, Cultured; D004705:Endocytosis; D004847:Epithelial Cells / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000378:metabolism; D009345:Neisseria meningitidis / Q000502:physiology*; D018272:Porins / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D018272:Porins; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D037521:Virulence Factors
keywords: Airway epithelial cells; Intracellular bacteria; PorB