Neisseriae internalization by epithelial cells is enhanced by TLR2 stimulation

Abstract

N. 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.

Staphylococcus aureus Internalized by Skin Keratinocytes Evade Antibiotic Killing

“…The concept of metabolically dormant and semi-dormant bacilli residing in host intracellular niches is not new. Neisseria meningitidis is known to be internalized by human airway epithelial cells through a mechanism also partly dependent on actin polymerization (Toussi et al, 2016). Mycobacteria tuberculosis survive and grow within macrophages, which provide a sanctuary protecting these bacteria from the bactericidal effects of some anti-tuberculous antibiotics (Jindani et al, 2003).…”

Interactions and Signal Transduction Pathways Involved during Central Nervous System Entry by Neisseria meningitidis across the Blood–Brain Barriers

“…Receptor interactions in choroid epithelial cells in vitro result in an NFκB-mediated pro-inflammatory immune response involving the transcription factor IκBζ as well as regnase, a ribonuclease involved in posttranscriptional regulation of the inflammatory immune response [ 127 , 139 ]. NFκB-mediated as well as MAPK signaling involved in internalization has also been reported for bronchial epithelial cells [ 131 ].…”

“…Expression analysis of pattern recognition receptors (PRRs) reveals TLR2/TLR6 complex interactions with lipoprotein components of the bacterial cell wall more likely than TLR2/TLR1- or TLR4-mediated signaling. Neisseria internalization into epithelial cells in vitro also seems rather to involve TLR2/TLR1 than TLR4 signaling [ 131 ]. The PorB protein of Neisseria is considered as a TLR2/TLR6 ligand [ 132 ].…”

Amyloid aggregates of the deubiquitinase OTUB1 are neurotoxic, suggesting that they contribute to the development of Parkinson's disease

“…Similar to A␤ and ␣-synuclein, OTUB1 oligomers also alter the membrane nanostructure, as observed in AFM. The membrane damage by amyloid oligomers is presumably due to the electrostatic interaction between protein assembly and lipid surfaces, as observed in many antimicrobial peptides (77,78). Neuronal cells exposed to amyloid oligomers show a disrupted actin cytoskeletal network compared with monomer.…”