Receptor‐mediated endocytosis of <i>Neisseria gonorrhoeae</i> into primary human urethral epithelial cells: the role of the asialoglycoprotein receptor

Harvey, Hillery A.; Jennings, Michael P.; Campbell, Colleen A.; Williams, Richard D.; Apicella, Michael A.

doi:10.1046/j.1365-2958.2001.02666.x

Cited by 109 publications

(73 citation statements)

References 81 publications

(169 reference statements)

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“…The tissue distribution of the major class of Opa protein adherence receptors, the human CEACAMs, does not correlate with the predominant sites of gonococcal infection in humans. For example, limited or no CEACAM expression was detected on primary male urethral epithelial cells (20) and some normal cervical and fallopian tube cells (59).…”

Section: Discussionmentioning

confidence: 99%

Opacity Proteins Increase Neisseria gonorrhoeae Fitness in the Female Genital Tract Due to a Factor under Ovarian Control

2010

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The neisserial opacity (Opa) proteins are a family of antigenically distinct outer membrane proteins that undergo phase-variable expression. Opa ؉ variants of Neisseria gonorrhoeae strain FA1090 are selected in a cyclical pattern from the lower genital tract of estradiol-treated mice. Here we show that cyclical recovery of Opa ؉ gonococci does not occur in ovariectomized mice; therefore, the reproductive cycle plays a role in the selection kinetics in vivo. As predicted by the selection pattern shown by wild-type gonococci, we demonstrated that a constitutive Opa-expressing strain was more fit than an Opa-deficient mutant in the early and late phases of infection. We found no evidence that Opa-mediated colonization selects for Opa ؉ variants during murine infection based on adherence assays with cultured murine epithelial cells. We also tested the hypothesis that complement selects for Opa protein expression during infection. Although some Opa ؉ variants of a serum-sensitive derivative of strain FA1090 were more resistant to the bactericidal activity of normal human serum, selection for Opa expression was not abrogated in C3-depleted mice. Finally, as previously reported, Opa ؉ gonococci were more sensitive to serine proteases. Thus, proteases or protease inhibitors may contribute to the observed in vivo selection pattern. We concluded that Opa proteins promote persistence of N. gonorrhoeae in the female genital tract and that opa gene phase variation allows gonococci to evade or capitalize upon unidentified host factors of the mammalian reproductive cycle. This work revealed an intimate interaction between pathogen and host and provides evidence that hormonally related factors shape bacterial adaptation.

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Section: Discussionmentioning

confidence: 99%

Opacity Proteins Increase Neisseria gonorrhoeae Fitness in the Female Genital Tract Due to a Factor under Ovarian Control

2010

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“…Gonococcal adhesion to urethral epithelia is mediated largely by LOS-asialogycoprotein receptor interactions [36], whereas adhesion to the Chang cell line is dependent upon Opa-heparin sulphate proteoglycan interactions [26]. While the observed effects on adhesion were relatively small, this does not preclude them from being of significance, particularly if they act in co-ordination with other host immune factors.…”

Section: Discussionmentioning

confidence: 99%

Mannose-binding lectin is present in human semen and modulates cellular adhesion of Neisseria gonorrhoeae in vitro

Wing

Jack

Lee

et al. 2009

Clinical and Experimental Immunology

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SummaryMannose-binding lectin (MBL) is an innate immune molecule present in blood and some mucosal tissues, which can influence microbial attachment and inflammatory responses of host cells during infection. In this study MBL was found to be present at a low concentration in semen samples in the range 1·2-24·9 ng/ml. Co-incubation of bacteria with semen resulted in the binding of MBL to the bacterial surface. Neisseria gonorrhoeae is a common cause of genitourinary infection. MBL bound to N. gonorrhoeae with strain-to-strain variation in the intensity of binding and nature of the bacterial receptor. Pretreatment with MBL concentrations similar to those found in human serum modulated the adhesion of N. gonorrhoeae strain FA1090 but not strain MS11 to epithelial cells. This effect was dose-dependent. This work demonstrates that MBL is present in human semen and modifies cellular responses to N. gonorrhoeae in a concentration-dependent manner.

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“…This protein could act as a soluble receptor for LOS and Opa on bacterial membranes if produced by cells in the local environment of gonococcal infection. The effect of soluble TREM-2 binding to these molecules remains to be investigated, but we can speculate that it might modulate their interaction with human cells as both LOS and Opa function as adhesins for several epithelial cell receptors (7,(44)(45)(46)(47). In addition, the binding of soluble TREM-2 to LOS and Opa may influence the binding and function of soluble proteins galectin-3 and mannose-binding lectin known to target LOS and Opa, respectively (27,32).…”

Section: Discussionmentioning

confidence: 99%

TREM-2 binds to lipooligosaccharides of Neisseria gonorrhoeae and is expressed on reproductive tract epithelial cells

et al. 2008

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Triggering receptor expressed on myeloid cells-2 (TREM-2) is an innate immune receptor that initiates cellular activation upon ligation. In this study, we examined the interaction of TREM-2 with Neisseria gonorrhoeae using murine TREM-2A as it has been reported to recognize bacterial ligands. Using a whole bacteria ELISA, TREM-2A bound to all 6 strains in variable degrees. Far western blots of gonococcal outer membranes revealed TREM-2A binding to lipooligosaccharide (LOS) and Opa protein with predominant binding to LOS. Binding of TREM-2A to LOS was confirmed by ELISA and surface plasmon resonance. O-deacylation of the lipid A significantly reduced binding. Flow cytometry and reporter cell assays showed that gonococci bound to TREM-2A-transfected cells and induced transmembrane signaling. In humans, TREM-2 was constitutively expressed by genitourinary and fallopian tube epithelial cells, both of which are primary targets of gonococcal invasion. Ligation of TREM-2 by LOS induced IL-6 production in HeLa cervical carcinoma cells. To our knowledge, this is the first report of the expression of human TREM-2 by cells deriving from a non-myeloid lineage. We conclude that gonococci can interact with TREM-2 receptors through binding to LOS and Opa protein and initiate cell signaling and cytokine production.

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Receptor‐mediated endocytosis of Neisseria gonorrhoeae into primary human urethral epithelial cells: the role of the asialoglycoprotein receptor

Cited by 109 publications

References 81 publications

Opacity Proteins Increase Neisseria gonorrhoeae Fitness in the Female Genital Tract Due to a Factor under Ovarian Control

Opacity Proteins Increase Neisseria gonorrhoeae Fitness in the Female Genital Tract Due to a Factor under Ovarian Control

Mannose-binding lectin is present in human semen and modulates cellular adhesion of Neisseria gonorrhoeae in vitro

TREM-2 binds to lipooligosaccharides of Neisseria gonorrhoeae and is expressed on reproductive tract epithelial cells

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