The host adherens junction molecule nectin-1 is downregulated in Chlamydia trachomatis-infected genital epithelial cells

Sun, Jesse; Kintner, Jennifer; Schoborg, Robert V.

doi:10.1099/mic.0.2007/015164-0

Cited by 19 publications

(25 citation statements)

References 56 publications

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“…As shown in Figure S1, both HeLa and HEC-1B cells express nectin-1 and nectin-2 transcripts, although to a lesser degree than CHO-nectin-1 or CHO-nectin-2 cells. Finally, Sun et al demonstrated that HeLa cells express nectin-1α protein and mRNA transcripts of all three isoforms (Nectin-1α, -1β, and -1γ) by RT-PCR (Sun et al, 2008). …”

Section: Resultsmentioning

confidence: 99%

“…The Western blot assays were conducted as described by Sun et al (2008). The total protein concentration in cell lysates was normalized by analysis of a SYPRO Ruby stain (Bio-Rad) using a G-box (Bio-Rad) and SynGene software.…”

Section: Methodsmentioning

confidence: 99%

“…Densitometry analysis was performed using a FX phosphorimager and Quantity One V2.5.0 software (Bio-Rad) or with a G-box and SynGene software (Biorad). To control for small variations in cell number and gel loading between sample lanes, the nectin-1 quantity in each sample was normalized to the amount of β-actin protein detected in that same lane (Sun et al, 2008). …”

Section: Methodsmentioning

confidence: 99%

“…Specific primers and synthetic control DNA targets for HVEM and nectin-2 were designed using Vector NTI Advance V10 (Invitrogen) and listed in Table S1. Nectin-1α, -1β, and -1γ specific primers and their oligonucleotide amplification controls were as previously described (Sun et al, 2008). Most reactions were performed using the following cycling conditions (unless otherwise indicated): 94°C, 1 min; 60°C, 1 min; 72°C, 1 min for 35 cycles.…”

Section: Methodsmentioning

confidence: 99%

“…Most reactions were performed using the following cycling conditions (unless otherwise indicated): 94°C, 1 min; 60°C, 1 min; 72°C, 1 min for 35 cycles. The resulting PCR products were electrophoresed and quantified as previously described (Sun et al, 2008). …”

Section: Methodsmentioning

confidence: 99%

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Host nectin-1 is required for efficient Chlamydia trachomatis serovar E development

Hall

Sun

Slade

et al. 2014

Front. Cell. Infect. Microbiol.

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Interaction of Herpes Simplex Virus (HSV) glycoprotein D (gD) with the host cell surface during Chlamydia trachomatis/HSV co-infection stimulates chlamydiae to become persistent. During viral entry, gD interacts with one of 4 host co-receptors: HVEM (herpes virus entry mediator), nectin-1, nectin-2 and 3-O-sulfated heparan sulfate. HVEM and nectin-1 are high-affinity entry receptors for both HSV-1 and HSV-2. Nectin-2 mediates HSV-2 entry but is inactive for HSV-1, while 3-O-sulfated heparan sulfate facilitates HSV-1, but not HSV-2, entry. Western blot and RT-PCR analyses demonstrate that HeLa and HEC-1B cells express nectin-1 and nectin-2, but not HVEM. Because both HSV-1 and HSV-2 trigger persistence, these data suggest that nectin-1 is the most likely co-receptor involved. Co-infections with nectin-1 specific HSV-1 mutants stimulate chlamydial persistence, as evidenced by aberrant body (AB) formation and decreased production of elementary bodies (EBs). These data indicate that nectin-1 is involved in viral-induced chlamydial persistence. However, inhibition of signal transduction molecules associated with HSV attachment and entry does not rescue EB production during C. trachomatis/HSV-2 co-infection. HSV attachment also does not activate Cdc42 in HeLa cells, as would be expected with viral stimulated activation of nectin-1 signaling. Additionally, immunofluorescence assays confirm that HSV infection decreases nectin-1 expression. Together, these observations suggest that gD binding-induced loss of nectin-1 signaling negatively influences chlamydial growth. Chlamydial infection studies in nectin-1 knockdown (NKD) HeLa cell lines support this hypothesis. In NKD cells, chlamydial inclusions are smaller in size, contain ABs, and produce significantly fewer infectious EBs compared to C. trachomatis infection in control HeLa cells. Overall, the current study indicates that the actions of host molecule, nectin-1, are required for successful C. trachomatis development.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Host nectin-1 is required for efficient Chlamydia trachomatis serovar E development

Hall

Sun

Slade

et al. 2014

Front. Cell. Infect. Microbiol.

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The role of epithelial tight junctions involved in pathogen infections

Yang

2014

Mol Biol Rep

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Tight junctions (TJs) are sealing complexes between adjacent epithelial cells, functioning by controlling paracellular passage and maintaining cell polarity. These functions of TJs are primarily based on structural integrity as well as dynamic regulatory balance, indicating plasticity of TJ in response to external stimuli. An indispensable role of TJs involved in pathogen infection has been widely demonstrated since disruption of TJs leads to a distinct increase in paracellular permeability and polarity defects which facilitate viral or bacterial entry and spread. In addition to pathological changes in TJ integrity, TJ proteins such as occludin and claudins can either function as receptors for pathogen entry or interact with viral/bacterial effector molecules as an essential step for characterizing an infective stage. This suggests a more complicated role for TJ itself and especially specific TJ components. Thus, this review surveys the role of the epithelial TJs involved in various pathogen infections, and extends TJ targeted therapeutic and pharmacological application prospects.

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The Chlamydia Protease CPAF Regulates Host and Bacterial Proteins to Maintain Pathogen Vacuole Integrity and Promote Virulence

Jørgensen

Bednar

Amin

et al. 2011

Cell Host & Microbe

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SUMMARY The obligate intracellular bacterial pathogen Chlamydia trachomatis injects numerous effector proteins into the epithelial cell cytoplasm to manipulate host functions important for bacterial survival. In addition, the bacterium secretes a serine protease, chlamydial protease-like activity factor (CPAF). Although several CPAF targets are reported, the significance of CPAF-mediated proteolysis is unclear due to the lack of specific CPAF inhibitors and the diversity of host targets. We report that CPAF also targets chlamydial effectors secreted early during the establishment of the pathogen-containing vacuole (“inclusion”). We designed a cell-permeable CPAF-specific inhibitory peptide and used it to determine that CPAF prevents superinfection by degrading early Chlamydia effectors translocated during entry into a pre-infected cell. Prolonged CPAF inhibition leads to loss of inclusion integrity and caspase-1-dependent death of infected epithelial cells. Thus, CPAF functions in niche protection, inclusion integrity and pathogen survival, making the development of CPAF-specific protease inhibitors an attractive anti-chlamydial therapeutic strategy.

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The host adherens junction molecule nectin-1 is downregulated in Chlamydia trachomatis-infected genital epithelial cells

Cited by 19 publications

References 56 publications

Host nectin-1 is required for efficient Chlamydia trachomatis serovar E development

Host nectin-1 is required for efficient Chlamydia trachomatis serovar E development

The role of epithelial tight junctions involved in pathogen infections

The Chlamydia Protease CPAF Regulates Host and Bacterial Proteins to Maintain Pathogen Vacuole Integrity and Promote Virulence

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