<i>Neisseria meningitidis</i> infection of human endothelial cells interferes with leukocyte transmigration by preventing the formation of endothelial docking structures

Doulet, Nicolas; Donnadieu, Emmanuel; Laran-Chich, Marie-Pierre; Niedergang, Florence; Nassif, Xavier; Bourdoulous, Sandrine

doi:10.1084/jem2036oia15

Cited by 19 publications

(33 citation statements)

References 10 publications

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“…Celli et al (40) demonstrate a functional requirement for the interaction between ICAM-1 and ␣-actinin 4 during leukocyte TEM. Similarly, sequestration of endothelial ezrin or moesin away from sites of leukocyte adhesion blocks formation of endothelial docking structures as well as leukocyte TEM (41,42).…”

Section: Discussionmentioning

confidence: 99%

ICAM-1-Mediated, Src- and Pyk2-Dependent Vascular Endothelial Cadherin Tyrosine Phosphorylation Is Required for Leukocyte Transendothelial Migration

Allingham

Buul

Burridge

2007

The Journal of Immunology

290

304

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Leukocyte transendothelial migration (TEM) has been modeled as a multistep process beginning with rolling adhesion, followed by firm adhesion, and ending with either transcellular or paracellular passage of the leukocyte across the endothelial monolayer. In the case of paracellular TEM, endothelial cell (EC) junctions are transiently disassembled to allow passage of leukocytes. Numerous lines of evidence demonstrate that tyrosine phosphorylation of adherens junction proteins, such as vascular endothelial cadherin (VE-cadherin) and β-catenin, correlates with the disassembly of junctions. However, the role of tyrosine phosphorylation in the regulation of junctions during leukocyte TEM is not completely understood. Using human leukocytes and EC, we show that ICAM-1 engagement leads to activation of two tyrosine kinases, Src and Pyk2. Using phospho-specific Abs, we show that engagement of ICAM-1 induces phosphorylation of VE-cadherin on tyrosines 658 and 731, which correspond to the p120-catenin and β-catenin binding sites, respectively. These phosphorylation events require the activity of both Src and Pyk2. We find that inhibition of endothelial Src with PP2 or SU6656 blocks neutrophil transmigration (71.1 ± 3.8% and 48.6 ± 3.8% reduction, respectively), whereas inhibition of endothelial Pyk2 also results in decreased neutrophil transmigration (25.5 ± 6.0% reduction). Moreover, overexpression of the nonphosphorylatable Y658F or Y731F mutants of VE-cadherin impairs transmigration of neutrophils compared with overexpression of wild-type VE-cadherin (32.7 ± 7.1% and 38.8 ± 6.5% reduction, respectively). Our results demonstrate that engagement of ICAM-1 by leukocytes results in tyrosine phosphorylation of VE-cadherin, which is required for efficient neutrophil TEM.

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Section: Discussionmentioning

confidence: 99%

ICAM-1-Mediated, Src- and Pyk2-Dependent Vascular Endothelial Cadherin Tyrosine Phosphorylation Is Required for Leukocyte Transendothelial Migration

Allingham

Buul

Burridge

2007

The Journal of Immunology

290

304

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“…Subsequent to the formation of these microcolonies, TFP elicit the organization of specific honeycomb-shaped molecular complexes underneath bacterial colonies, referred to as "cortical plaques." Cortical plaques result from the recruitment of molecular linkers, such as ezrin and moesin, adhesion molecules, membrane receptors, and polymerized cortical actin (9,18). The formation of the cortical plaque is associated with the recruitment of intercellular junction molecules at the site of bacterium-host cell interaction, thus leading to the depletion of junction proteins at the cell-cell interface, the opening of intercellular junctions, and the subsequent crossing of the blood-brain barrier (BBB) (5).…”

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confidence: 99%

The Meningococcal Minor Pilin PilX Is Responsible for Type IV Pilus Conformational Changes Associated with Signaling to Endothelial Cells

et al. 2012

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ABSTRACTNeisseria meningitidiscrosses the blood-brain barrier (BBB) following the activation of the β2-adrenergic receptor by the type IV pili (TFP). Two components of the type IV pili recruit the β2-adrenergic receptor, the major pilin PilE and the minor pilin PilV. Here, we report that a strain deleted of PilX, one of the three minor pilins, is defective in endothelial cell signaling. The signaling role of PilX was abolished when pili were not retractable. Purified PilX was unable to recruit the β2-adrenergic receptor, thus suggesting that PilX was playing an indirect role in endothelial cell signaling. Considering the recent finding that type IV pili can transition into a new conformation (N. Biais, D. L. Higashi, J. Brujic, M. So, and M. P. Sheetz, Proc. Natl. Acad. Sci. U. S. A. 107:11358–11363, 2010), we hypothesized that PilX was responsible for a structural modification of the fiber and allowed hidden epitopes to be exposed. To confirm this hypothesis, we showed that a monoclonal antibody which recognizes a linear epitope of PilE bound fibers only when bacteria adhered to endothelial cells. On the other hand, this effect was not observed in PilX-deleted pili. A deletion of a region of PilX exposed on the surface of the fiber had phenotypical consequences identical to those of a PilX deletion. These data support a model in which surface-exposed motifs of PilX use forces generated by pilus retraction to promote conformational changes required for TFP-mediated signaling.

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“…The first group included children (n ϭ 155) aged 6 (27). Blood was obtained 8 months after the last priming dose and prior to boosting at a mean of 1.05 years (range, 361 to 425 days) after immunization.…”

Section: Methodsmentioning

confidence: 99%

Single Nucleotide Polymorphisms in the Toll-Like Receptor 3 and CD44 Genes Are Associated with Persistence of Vaccine-Induced Immunity to the Serogroup C Meningococcal Conjugate Vaccine

Moore

Hennig

Perrett

et al. 2011

Clin. Vaccine Immunol.

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fThe rate of decay of antibody concentration following serogroup C meningococcal (MenC) polysaccharide-protein conjugate vaccination varies between individuals. This depends partly on vaccination age but may be influenced by human genetics. We studied 721 single nucleotide polymorphisms (SNPs) across 131 candidate genes in a first cohort of 905 Caucasians (11 to 21 years old; mean time after vaccination, 4.9 years) and 30 SNPs across 17 genes in a replication study using 155 children, aged 6 to 12 years (mean time after vaccination, 6.7 years), and 196 infants (1 year old; mean time after vaccination, 8 months). Individuals were classified as responders or nonresponders for total MenC IgG concentration and MenC serum bactericidal antibody (SBA) measurements. Associated genes were examined further for quantitative outcome measures. Fifty-nine SNPs in 37 genes were associated with IgG persistence (adjusted for age at measurement), and 56 SNPs in 36 genes were associated with SBA persistence (adjusted for age at measurement and vaccine used). Three SNPs each within the Toll-like receptor 3 (TLR3) (rs3775291, rs3775292, and rs5743312) and CD44 (rs11033013, rs353644, and rs996076) genes were associated with IgG (adjusted for age at measurement) or SBA (adjusted for age at measurement and vaccine used) persistence in the initial genetic study (P, 0.02 to 0.04). Single SNPs within the TLR3 (rs7657186) (P ‫؍‬ 0.004 [unadjusted]) and CD44 (rs12419062) (P ‫؍‬ 0.01 [unadjusted]) genes were associated with IgG persistence in the replication study. These results suggest that genetic polymorphisms in the TLR3 and CD44 genes are associated with the persistence of the immune response to MenC vaccines 1 to 6 years after vaccination.

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Neisseria meningitidis infection of human endothelial cells interferes with leukocyte transmigration by preventing the formation of endothelial docking structures

Abstract: Abbreviations used in this paper: ERM, ezrin-radixin-moesin; HBMEC, human bone marrow endothelial cell line; ICAM, intracellular adhesion molecule; SDF, stromal cell-derived factor; VCAM, vascular cell adhesion molecule.The online version of this article contains supplemental material.

Cited by 19 publications

References 10 publications

ICAM-1-Mediated, Src- and Pyk2-Dependent Vascular Endothelial Cadherin Tyrosine Phosphorylation Is Required for Leukocyte Transendothelial Migration

ICAM-1-Mediated, Src- and Pyk2-Dependent Vascular Endothelial Cadherin Tyrosine Phosphorylation Is Required for Leukocyte Transendothelial Migration

The Meningococcal Minor Pilin PilX Is Responsible for Type IV Pilus Conformational Changes Associated with Signaling to Endothelial Cells

Single Nucleotide Polymorphisms in the Toll-Like Receptor 3 and CD44 Genes Are Associated with Persistence of Vaccine-Induced Immunity to the Serogroup C Meningococcal Conjugate Vaccine

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