Syndecan-1 and syndecan-4 can mediate the invasion of OpaHSPG-expressing Neisseria gonorrhoeae into epithelial cells

Freissler, Elke; Heyde, Alexander; Gourichon, David; Meyer, Thomas; Dehio, Christoph

doi:10.1046/j.1462-5822.2000.00036.x

Cited by 93 publications

(77 citation statements)

References 52 publications

(63 reference statements)

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“…50 Certain members of this family are transmembrane proteoglycans 50 that indirectly interact with actin filaments. 51 These molecules might be the link between the nanoparticles and the actin filaments, a possibility that we are currently investigating. The Retrograde Pathway Brings a New Mechanism by Which Positive Surface Charge Supports Particle Recruitment and Potential Subsequent Toxicity.…”

Section: Resultsmentioning

confidence: 99%

Submicrometer and Nanoscale Inorganic Particles Exploit the Actin Machinery To Be Propelled along Microvilli-like Structures into Alveolar Cells

et al. 2007

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The growing commerce in micro- and nanotechnology is expected to increase human exposure to submicrometer and nanoscale particles, including certain forms of amorphous silica. When inhaled, these particles are likely to reach the alveoli, where alveolar type II epithelial cells that are distinguished by apical microvilli are found. These cells play critical roles in the function of the alveoli and participate in the immune response to amorphous silica and other particles by releasing chemokines. The cellular interactions of the particles, which drive the cellular responses, are still unclear. Adverse effects of nanoparticles have been attributed, in part, to the unique properties of materials at the nanoscale. However, little is known about the cellular interactions of individual or small nanoparticle aggregates, mostly because of their tendency to agglomerate under experimental conditions. Here we investigate the interaction and internalization pathway of individual precipitated amorphous silica particles with specific surface properties and size, by following one particle at a time. We find that both 100 and 500 nm particles can take advantage of the actin turnover machinery within filopodia and microvilli-like structures to advance their way into alveolar type II epithelial cells. This pathway is strictly dependent on the positive surface charge of the particle and on the integrity of the actin filaments, unraveling the coupling of the particle with the intracellular environment across the cell membrane. The retrograde pathway brings a new mechanism by which positive surface charge supports particle recruitment, and potential subsequent toxicity, by polarized epithelial cells bearing microvilli.

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Section: Resultsmentioning

confidence: 99%

Submicrometer and Nanoscale Inorganic Particles Exploit the Actin Machinery To Be Propelled along Microvilli-like Structures into Alveolar Cells

et al. 2007

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“…7C) (57)(58)(59). Heparin, an anticoagulant GAG, is composed of repeating disaccharide units of D-glucosamine and uronic acid linked by ␣134 interglycosidic bonds.…”

Section: Discussionmentioning

confidence: 99%

Crystal Structure of the N-terminal Domain of the Group B Streptococcus Alpha C Protein

Auperin

Bolduc

Baron

et al. 2005

Journal of Biological Chemistry

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Group B Streptococcus (GBS) is the leading cause of bacterial pneumonia, sepsis, and meningitis among neonates and an important cause of morbidity among pregnant women and immunocompromised adults. Invasive diseases due to GBS are attributed to the ability of the pathogen to translocate across human epithelial surfaces. The alpha C protein (ACP) has been identified as an invasin that plays a role in internalization and translocation of GBS across epithelial cells. The soluble N-terminal domain of ACP (NtACP) blocks the internalization of GBS. We determined the 1.86-Å resolution crystal structure of NtACP comprising residues Ser 52 through Leu 225 of the full-length ACP. NtACP has two domains, an N-terminal ␤-sandwich and a C-terminal three-helix bundle. Structural and topological alignments reveal that the ␤-sandwich shares structural elements with the type III fibronectin fold (FnIII), but includes structural elaborations that make it unique. We have identified a potential integrin-binding motif consisting of Lys-Thr-Asp 146 , Arg 110 , and Asp 118 . A similar arrangement of charged residues has been described in other invasins. ACP shows a heparin binding activity that requires NtACP. We propose a possible heparin-binding site, including one surface of the three-helix bundle, and nearby portions of the sandwich and repeat domains. We have validated this prediction using assays of the heparin binding and cell-adhesion properties of engineered fragments of ACP. This is the first crystal structure of a member of the highly conserved Gram-positive surface alpha-like protein family, and it will enable the internalization mechanism of GBS to be dissected at the atomic level.Group B Streptococcus (GBS) 1 (Streptococcus agalactiae) remains the leading cause of invasive bacterial diseases in neonates, despite its decline in prevalence during the last decade because of intrapartum chemoprophylatic therapy (1, 2). It is also an important cause of morbidity in pregnant women and non-pregnant adults with underlying medical conditions (3-5). GBS colonizes the human gastrointestinal and genitourinary tracts and may cause chorioamnionitis and urinary tract infection in pregnant women and a range of invasive infections in elderly and immunocompromised adults (1, 6 -8). During labor and delivery, GBS may be transmitted to neonates, causing pneumonia, sepsis, or meningitis. Four to six percent of all neonatal GBS infections result in death (6, 9). In vitro, GBS adheres to (10, 11), internalizes within (12-14), and translocates across (15) intact human epithelial and endothelial cells. Little is known about the bacterial components that allow this pathogen to adhere to and penetrate cellular membranes. Previous studies suggest that surface proteins are significantly involved in the process (11, 16). The surface-expressed GBS alpha C protein (ACP) has been shown to act as an invasin (15). ACP is the prototype of a family of surface-expressed proteins containing long tandem repeats (alpha-like proteins (Alp)). Members of this famil...

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“…Although certain Opa variants bind to heparan sulfate proteoglycan receptors (13)(14)(15), most are specific for members of the carcinoembryonic Ag-related cellular adhesion molecule (CEACAM) family of receptors (16 -22). CEACAMs are members of the Ig superfamily consisting of an amino-terminal Ig variable domain-like region followed by a variable number of Ig constant-like domains.…”

Section: Espite the Availability Of Effective Antibiotic Therapiesmentioning

confidence: 99%

CEACAM1 Dynamics during Neisseria gonorrhoeae Suppression of CD4+ T Lymphocyte Activation

Lee

Ostrowski

Gray-Owen

2008

The Journal of Immunology

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Neisseria gonorrhoeae colony opacity-associated (Opa) proteins bind to human carcinoembryonic antigen cellular adhesion molecules (CEACAM) found on host cells including T lymphocytes. Opa binding to CEACAM1 suppresses the activation of CD4+ T cells in response to a variety of stimuli. In this study, we use primary human CD4+ T cells isolated from peripheral blood to define the molecular events occurring subsequent to Opa-CEACAM1 binding. We establish that, in contrast to other cell types, T cells do not engulf N. gonorrhoeae upon CEACAM1 binding. Instead, the bacteria recruit CEACAM1 from intracellular stores and maintain it on the T cell surface. Upon TCR ligation, the co-engaged CEACAM1 becomes phosphorylated on tyrosine residues within the ITIMs apparent in the cytoplasmic domain. This allows the recruitment and subsequent activation of the src homology domain 2-containing tyrosine phosphatases SHP-1 and SHP-2 at the site of bacterial attachment, which prevents the normal tyrosine phosphorylation of the CD3ζ-chain and ZAP-70 kinase in response to TCR engagement. Combined, this dynamic response allows the bacteria to effectively harness the coinhibitory function of CEACAM1 to suppress the adaptive immune response at its earliest step.

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Syndecan-1 and syndecan-4 can mediate the invasion of OpaHSPG-expressing Neisseria gonorrhoeae into epithelial cells

Cited by 93 publications

References 52 publications

Submicrometer and Nanoscale Inorganic Particles Exploit the Actin Machinery To Be Propelled along Microvilli-like Structures into Alveolar Cells

Submicrometer and Nanoscale Inorganic Particles Exploit the Actin Machinery To Be Propelled along Microvilli-like Structures into Alveolar Cells

Crystal Structure of the N-terminal Domain of the Group B Streptococcus Alpha C Protein

CEACAM1 Dynamics during Neisseria gonorrhoeae Suppression of CD4+ T Lymphocyte Activation

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