Differential Gene Expression during Meningeal-Meningococcal Interaction: Evidence for Self-Defense and Early Release of Cytokines and Chemokines

Wells, Damien B.; Tighe, Patrick J.; Wooldridge, Karl G.; Robinson, Karen; Aldeen, Dlawer Ala '

doi:10.1128/iai.69.4.2718-2722.2001

Cited by 45 publications

(43 citation statements)

References 51 publications

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“…However, absent from the transcriptional profile was IL-1␤, which is involved in the pathogenesis of bacterial meningitis. The absence of elevated IL-1␤ transcripts in infected HBMEC was already observed in meningeal cells (64). Other infection-induced HBMEC genes specifically involved in neutrophil recruitment were the ICAM-1 gene, which, when up-regulated, leads to enhanced adhesion of neutrophils to the brain endothelium (14,15,32).…”

Section: Discussionmentioning

confidence: 90%

“…In general, the host defense against the pathogen includes cytokines, chemokines, and oxidative burst. Among the genes expressed following infection, we found genes involved in the immunological responses, such as those encoding IL-6 and TNF-␣, both described to be induced after N. meningitidis infection (7,51,57,64). However, absent from the transcriptional profile was IL-1␤, which is involved in the pathogenesis of bacterial meningitis.…”

Section: Discussionmentioning

confidence: 94%

“…IL-6 and TNF-␣ have already been shown to be induced by N. meningitidis upon infection of meningothelial and endothe- lial cells (51,53,64). To analyze whether changes in mRNA levels were reflected in protein expression, ELISAs were performed for the detection of IL-6 and TNF-␣ protein secretion.…”

Section: Resultsmentioning

confidence: 99%

“…Wells et al used cDNA arrays to identify a cytoprotective response to N. meningitidis in meningothelial cells (64). The same group also profiled gene expression in meningothelial cells in response to secreted meningococcal proteins (51).…”

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confidence: 99%

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Gene Expression Pattern in Human Brain Endothelial Cells in Response to Neisseria meningitidis

et al. 2007

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To extend our knowledge of target proteins in endothelial cells infected with the meningitis-causing pathogen Neisseria meningitidis, we characterized the interaction between the bacterial and human brain microvascular endothelial cell (HBMEC) monolayers. By use of human cDNA microarrays, transcriptional analysis revealed distinct responses to 4 and 8 h of infection. We also addressed the question of whether the major virulence factor of meningococci, i.e., the capsule, influences the host cell response. Of the 1,493 (at 4 h postinfection) and 1,246 (at 8 h postinfection) genes with altered expression upon bacterial contact, about 49.4% and 45%, respectively, depended on capsule expression. In particular, we identified an increase of expression for genes encoding proteins involved in bacterial adhesion and invasion. High levels of apoptosis-related gene (bad, bak, asp, and immediate-early response gene 1) expression could also be detected in infected cells. Further analyses confirmed that HBMECs displayed several hallmarks of apoptosis in response to N. meningitidis infection, namely, phosphatidylserine translocation and activation of caspase 3 and AMP-activated protein kinase ␣. Moreover, several differentially regulated genes not previously known to respond to meningococcal infection were identified. Of these, genes encoding cell adhesion proteins (CD44, CD98, and CD99), genes involved in downstream signaling of integrins (integrin-linked kinase, mitogen-activated protein kinase kinase 1, and mitogen-activated protein kinase kinase kinase 10) as well as negative regulators of these pathways (dualspecificity phosphatases 1, 5, and 14 and G protein pathway suppressor 2), and genes involved in cytoskeleton reorganization (those encoding Arp2/3, p34-arc, actinin alpha 1, vasodilatator-stimulated protein, and Wiskott-Aldrich syndrome protein) were the most prominent. This global transcriptional analysis creates a new platform for further molecular and cellular analysis of the interaction between N. meningitidis and target cells.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Gene Expression Pattern in Human Brain Endothelial Cells in Response to Neisseria meningitidis

et al. 2007

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“…cDNA arrays were used to profile gene expression in meningothelial cells in response to interaction with N. meningitidis or to secreted meningococcal proteins [38,39]. In addition, they were used in epithelial cells to compare responses towards piliated and nonpiliated N. gonorrhoeae cells and piliated encapsulated meningococci [40].…”

Section: Transcriptomicsmentioning

confidence: 99%

Post-genomics ofNeisseria meningitidis: an update

Bernardini¹,

Braconi²,

Lusini³

et al. 2011

Expert Review of Proteomics

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Post‐genomic virology: the impact of bioinformatics, microarrays and proteomics on investigating host and pathogen interactions

Kellam

2001

Reviews in Medical Virology

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Post-genomic research encompasses many diverse aspects of modern science. These include the two broad subject areas of computational biology (bioinformatics) and functional genomics. Laboratory based functional genomics aims to measure and assess either the messenger RNA (mRNA) levels (transcriptome studies) or the protein content (proteome studies) of cells and tissues. All of these methods have been applied recently to the study of host and pathogen interactions for both bacteria and viruses. A basic overview of the technology is given in this review together with approaches to data analysis. The wealth of information produced from even these preliminary studies has shown the generalities, subtleties and specificities of host-pathogen interactions. Such research should ultimately result in new methods for diagnosing and treating infectious diseases.

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Differential Gene Expression during Meningeal-Meningococcal Interaction: Evidence for Self-Defense and Early Release of Cytokines and Chemokines

Cited by 45 publications

References 51 publications

Gene Expression Pattern in Human Brain Endothelial Cells in Response to Neisseria meningitidis

Gene Expression Pattern in Human Brain Endothelial Cells in Response to Neisseria meningitidis

Post-genomics ofNeisseria meningitidis: an update

Post‐genomic virology: the impact of bioinformatics, microarrays and proteomics on investigating host and pathogen interactions

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