Secreted proteins from Neisseria meningitidis mediate differential human gene expression and immune activation

Cellular Microbiology
K RobinsonDlawer A A Ala'Aldeen

Abstract

Meningococcal secreted proteins (MSPs) have been poorly characterized. We hypothesized that MSPs play essential roles in host--bacterial interactions and in the pathogenesis of disease. In order to test this, we examined differential host gene expression in human meningeal-derived cells, in response to endotoxin-depleted MSPs compared to live bacteria. Using expression arrays, upregulated expression of several pro-inflammatory and apoptosis-related genes was found to be induced by MSPs. The transcription and translation of representative genes was confirmed by using various methods. Increased interleukin 8 (IL-8) and cyclooxygenase 2 (COX-2) gene transcription was confirmed using real-time PCR. Upregulated IL-8, IL-6, ICAM-1 and COX-2 protein expression were confirmed by ELISA, flow cytometry or Western immunoblots. Furthermore, exposure of cells to MSPs or live meningococci induced a small significant resistance effect to staurosporine-induced apoptosis. Secreted meningococcal virulence factors are therefore important in inducing host inflammatory responses and resistance to apoptosis, and they are worthy of extensive investigation.

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Citations

Nov 30, 2006·Infection and Immunity·Alexandra Schubert-UnkmeirMatthias Frosch
Aug 23, 2005·Infection and Immunity·Karl G WooldridgeDlawer A A Ala'aldeen
May 30, 2008·Journal of Clinical Microbiology·Martin J CallaghanAndrew J Pollard
May 26, 2011·PloS One·Xiaorong XinAlbert Neutzner
May 12, 2009·Vaccine·Yanwen LiDlawer A A Ala'aldeen
Jun 15, 2005·Cellular Microbiology·Peter BergmanBirgitta Agerberth
Sep 13, 2006·Cellular Microbiology·Neil J OldfieldDlawer A A Ala'Aldeen
Feb 14, 2006·FEMS Microbiology Reviews·Peter van Ulsen, Jan Tommassen
Jan 17, 2017·Nature Immunology·Robyn S KleinNicole Howard
Nov 10, 2009·Expert Review of Molecular Diagnostics·Alexandra Schubert-UnkmeirMatthias Frosch
Jan 1, 2020·Evolution; International Journal of Organic Evolution·Clarissa HouseJohn Hunt
Jun 18, 2010·Proceedings. Biological Sciences·Lukasz MichalczykMatthew J G Gage
Nov 18, 2011·Expert Review of Proteomics·Giulia BernardiniAnnalisa Santucci
Apr 24, 2009·Expert Review of Proteomics·Giulia BernardiniAnnalisa Santucci

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis