Interactions of Neisseria gonorrhoeae with human neutrophils.

Rest, R F; Shafer, W M

doi:10.1128/cmr.2.suppl.s83-s91.1989

Cited by 18 publications

(21 citation statements)

References 82 publications

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“…We observed that mobilization of both primary and secondary granules in response to CEACAM3-dependent signals was Syk dependent. It has been shown that PMN killing of N. gonorrhoeae is mediated by azurophilic granule proteins, specifically the cationic antimicrobial protein cathepsin G (Shafer et al, 1986) and neutrophil elastase (Rest and Shafer, 1989). While a link between Syk and degranulation has not been previously established, we have observed that CEACAM3-dependent degranulation and oxidative burst both require Syk.…”

Section: Discussionmentioning

confidence: 39%

“…The hallmark of infection by the human-restricted pathogen Neisseria gonorrhoeae (Ngo, gonococcus) is the appearance of a urethral or cervical exudate consisting of polymorphonuclear neutrophils (PMNs) associated with Gram-negative diplococci (Rest and Shafer, 1989). This interaction is opsonin-independent, and depends on bacterial expression of the colony opacity-associated (Opa) proteins, which allow PMNs to effectively recognize, engulf and kill the pathogen (Virji and Heckels, 1986;Kupsch et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

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The specific innate immune receptor CEACAM3 triggers neutrophil bactericidal activities via a Syk kinase-dependent pathway

Sarantis¹,

Gray-Owen²

2007

Cellular Microbiology

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SummaryThe human-restricted pathogens Neisseria gonorrhoeae, Neisseria meningitidis, Haemophilus influenzae and Moraxella catarrhalis colonize host tissues via carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs). One such receptor, CEACAM3, acts in a host-protective manner by orchestrating the capture and engulfment of invasive bacteria by human neutrophils. Herein, we show that bacterial binding to CEACAM3 causes recruitment of the cytoplasmic tyrosine kinase Syk, resulting in the phosphorylation of both CEACAM3 and Syk. This interaction is specific for the immunoreceptor tyrosine-based activation motif (ITAM) in the CEACAM3 cytoplasmic domain. While dispensable for the phagocytic uptake of single bacteria by CEACAM3, Syk is necessary for internalization when cargo size increases or when the density of CEACAMbinding ligand on the cargo surface is below a critical threshold. Moreover, Syk engagement is required for an effective bacterial killing response, including the neutrophil oxidative burst and degranulation functions in response to N. gonorrhoeae. These data reveal CEACAM3 as a specific innate immune receptor that mediates the opsonin-independent clearance of CEACAM-binding bacteria via Syk, a molecular trigger for functional immunoreceptor responses of both the adaptive (TCR, BCR, FcR) and innate (Dectin-1, CEACAM3) immune systems.

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Section: Discussionmentioning

confidence: 39%

Section: Introductionmentioning

confidence: 99%

The specific innate immune receptor CEACAM3 triggers neutrophil bactericidal activities via a Syk kinase-dependent pathway

Sarantis¹,

Gray-Owen²

2007

Cellular Microbiology

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“…Selection for Opa+ Gc occurs in naturally and experimentally infected individuals and in the female mouse genital tract (James and Swanson, ; Jerse, ; Cole et al ., ; Hobbs et al ., ). However, Opa+ Gc is more readily killed by PMNs (Rest et al ., 1982; 1985; Virji and Heckels, ; Fischer and Rest, ; Rest and Shafer, ; Sarantis and Gray‐Owen, ; Criss et al ., ; Ball and Criss, ). Therefore, Opa protein expression would be both advantageous and disadvantageous during gonorrhoeal infection.…”

Section: Discussionmentioning

confidence: 99%

“…Together, these results would suggest there is a disadvantage to Gc expressing CEACAM‐binding Opa proteins during infection. In support of this notion, Opa+ Gc have decreased survival compared with Opa− Gc in human PMNs (Rest et al ., 1982; 1985; Virji and Heckels, ; Fischer and Rest, ; Rest and Shafer, ; Sarantis and Gray‐Owen, ; Criss et al ., ; Ball and Criss, ). However, the precise mechanism leading to this survival defect is not yet defined.…”

Section: Introductionmentioning

confidence: 99%

Opa+Neisseria gonorrhoeaeexhibits reduced survival in human neutrophils via Src family kinase-mediated bacterial trafficking into mature phagolysosomes

et al. 2014

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Summary During gonorrheal infection, there is a heterogeneous population of Neisseria gonorrhoeae (Gc) varied in their expression of opacity-associated (Opa) proteins. While Opa proteins are important for bacterial attachment and invasion of epithelial cells, Opa+ Gc has a survival defect after exposure to neutrophils. Here, we use constitutively Opa- and OpaD+ Gc in strain background FA1090 to show that Opa+ Gc is more sensitive to killing inside adherent, chemokine-treated primary human neutrophils due to increased bacterial residence in mature, degradative phagolysosomes that contain primary and secondary granule antimicrobial content. Although Opa+ Gc stimulates a potent oxidative burst, neutrophil killing of Opa+ Gc was instead attributable to non-oxidative components, particularly neutrophil proteases and the bactericidal/permeability-increasing protein. Blocking interaction of Opa+ Gc with carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) or inhibiting Src family kinase signaling, which is downstream of CEACAM activation, enhanced the survival of Opa+ Gc in neutrophils. Src family kinase signaling was required for fusion of Gc phagosomes with primary granules to generate mature phagolysosomes. Conversely, ectopic activation of Src family kinases or coinfection with Opa+ Gc resulted in decreased survival of Opa- Gc in neutrophils. From these results, we conclude that Opa protein expression is an important modulator of Gc survival characteristics in neutrophils by influencing phagosome dynamics and thus bacterial exposure to neutrophils’ full antimicrobial arsenal.

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“…Controversy exists regarding the efficiency with which GC are killed by human PMNs (Casey etai, 1983;Parsons ef a/., 1985;Rest and Shafer, 1989;Rest, 1969: Smith, 1990), We showed that anti-nrPor sera increased binding of GC to PMNs and activated the oxidative burst, but anti-nrPor IgG did not result in killing of GC by PMNs, In control phagocytic killing experiments using S. aureus opsonized with 5% NHS, the presence of gonococci in the phagocytic mixture did not inhibit the killing of S. aureus. Phagocytic killing of GC has been correlated with binding of complement components and bound C3b or C3bi interactions with their respective PMN receptors (Wetzler ef ai, 1992b), We showed fhat some form of C'3 was deposited onto the gonococcai membrane in fhe presence of anti-nrPor IgG or mAbs, but the exact nature and configuration of the bound C'3 was not known.…”

Section: Discussionmentioning

confidence: 99%

Immunobiology of purified recombinant outer membrane porin protein I of Neisseria gonorrhoeae

Elkins

Kb²,

et al. 1994

Molecular Microbiology

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Gonococcal porins (Por) from strains FA19 (Por-1, serogroup A), MS11 (Por-2, serogroup B) and FA6434 (Por-5, a hybrid porin containing epitopes from both serogroups), were expressed in Escherichia coli and purified under non-denaturing conditions. Porins were inserted into liposomes, and they were bound by monoclonal antibodies which bind native Por and intact gonococci, but not denatured Por. All three recombinant porins (rPor) were highly immunogenic in rabbits without additional adjuvant. The rPor antisera were specific for Por by Western blotting and whole-cell radioimmunoprecipitation and were broadly cross-reactive within serogroups. Post-immune, but not pre-immune, sera bound to intact gonococci, induced deposition of complement components C3 and C9 onto gonococcal membranes and increased association with and activation of human neutrophils. Gonococci were not killed in bactericidal assays, and there was no phagocytic killing with gonococci opsonized with recombinant antisera. Lack of killing in bactericidal assays was not caused by the presence of blocking antibodies to the outer-membrane protein Rmp.

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Interactions of Neisseria gonorrhoeae with human neutrophils.

Cited by 18 publications

References 82 publications

The specific innate immune receptor CEACAM3 triggers neutrophil bactericidal activities via a Syk kinase-dependent pathway

The specific innate immune receptor CEACAM3 triggers neutrophil bactericidal activities via a Syk kinase-dependent pathway

Opa+Neisseria gonorrhoeaeexhibits reduced survival in human neutrophils via Src family kinase-mediated bacterial trafficking into mature phagolysosomes

Immunobiology of purified recombinant outer membrane porin protein I of Neisseria gonorrhoeae

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