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

Robinson, Karen; Taraktsoglou, Maria; Rowe, Kherie S J; Wooldridge, Karl G.; Ala’Aldeen, Dlawer A. A.

doi:10.1111/j.1462-5822.2004.00410.x

Cited by 28 publications

(28 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 95%

“…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). Binnicker and coworkers found up-regulation of several host antiapoptotic factors in urethral epithelial cells infected with Neisseria gonorrhoeae, a close relative of meningococci (3).…”

mentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2007

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2007

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

“…Its clinical severity is likely to be dependent on host and bacterial factors that influence the inflammatory and immunological responses of the host (9,12). A variety of meningococcal surface and secreted proteins play roles in contact with host cells (30), and some of these regulate host immunological responses (1,35). Few studies have investigated the distribution of the proteins involved in these interactions in the meningococcal population or their effects on clinical severity of invasive disease.…”

mentioning

confidence: 99%

Opa Protein Repertoires of Disease-Causing and Carried Meningococci

et al. 2008

View full text Add to dashboard Cite

The meningococcal Opa proteins play an important role in pathogenesis by mediating invasion of human cells. The aim of this investigation was to determine whether carried and disease-associated meningococci possess different Opa repertoires and whether the diversity of these proteins is associated with clinical severity of disease. Opa repertoires in 227 disease-associated meningococci, isolated in the United Kingdom over a period of 6 years, were compared to the repertoires in 190 asymptomatically carried meningococci isolated in the United Kingdom from a contemporary, nonepidemic period. Multidimensional scaling (MDS) was employed to investigate the association between Opa repertoires and multilocus sequence typing (MLST) genotypes. Associations with clinical severity were also analyzed statistically. High levels of diversity were observed in opa alleles, variable regions, and repertoires, and MDS revealed that MLST genotypes were strongly associated with particular Opa repertoires. Individual Opa proteins or repertoires were not associated with clinical severity, though there was a trend toward an association with the opaD locus. Meningococcal Opa repertoire is strongly linked to MLST genotype irrespective of epidemiological sampling and therefore correlates with invasiveness. It is not, however, strongly associated with severity of meningococcal disease.

show abstract

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

Cited by 28 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

Opa Protein Repertoires of Disease-Causing and Carried Meningococci

Contact Info

Product

Resources

About