A pilot study to show that asymptomatic sexually transmitted infections alter the foreskin epithelial proteome
There is limited data on the role of asymptomatic STIs (aSTIs) on the risk of human immunodeficiency virus (HIV) acquisition in the male genital tract (MGT). The impact of foreskin removal on lowering HIV acquisition is well described, but molecular events leading to HIV acquisition are unclear. Her...
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Frontiers Media S.A.
2022-10-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.928317/full |
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author | Nyaradzo T. L. Chigorimbo-Murefu Matthys Potgieter Matthys Potgieter Sonwabile Dzanibe Zikhona Gabazana Gershom Buri Aditya Chawla Bokani Nleya Abraham J. Olivier Rushil Harryparsad Bridget Calder Shaun Garnett Lungile Maziya David A. Lewis David A. Lewis Heather Jaspan Heather Jaspan Heather Jaspan Doug Wilson Jo-Ann S. Passmore Nicola Mulder Jonathan Blackburn Linda-Gail Bekker Clive M. Gray Clive M. Gray |
author_facet | Nyaradzo T. L. Chigorimbo-Murefu Matthys Potgieter Matthys Potgieter Sonwabile Dzanibe Zikhona Gabazana Gershom Buri Aditya Chawla Bokani Nleya Abraham J. Olivier Rushil Harryparsad Bridget Calder Shaun Garnett Lungile Maziya David A. Lewis David A. Lewis Heather Jaspan Heather Jaspan Heather Jaspan Doug Wilson Jo-Ann S. Passmore Nicola Mulder Jonathan Blackburn Linda-Gail Bekker Clive M. Gray Clive M. Gray |
author_sort | Nyaradzo T. L. Chigorimbo-Murefu |
collection | DOAJ |
description | There is limited data on the role of asymptomatic STIs (aSTIs) on the risk of human immunodeficiency virus (HIV) acquisition in the male genital tract (MGT). The impact of foreskin removal on lowering HIV acquisition is well described, but molecular events leading to HIV acquisition are unclear. Here, in this pilot study, we show that asymptomatic urethral infection with Chlamydia trachomatis (CT) significantly impacts the foreskin proteome composition. We developed and optimized a shotgun liquid chromatography coupled tandem mass spectrometry (MS)-based proteomics approach and utilized this on foreskins collected at medical male circumcision (MMC) from 16 aSTI+ men and 10 age-matched STI- controls. We used a novel bioinformatic metaproteomic pipeline to detect differentially expressed (DE) proteins. Gene enrichment ontology analysis revealed proteins associated with inflammatory and immune activation function in both inner and outer foreskin from men with an aSTI. Neutrophil activation/degranulation and viral-evasion proteins were significantly enriched in foreskins from men with aSTI, whereas homotypic cell–cell adhesion proteins were enriched in foreskin tissue from men without an aSTI. Collectively, our data show that asymptomatic urethral sexually transmitted infections result in profound alterations in epithelial tissue that are associated with depletion of barrier integrity and immune activation. |
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spelling | doaj.art-b8d07edb4fab4debb36db34c662f57862022-12-22T04:31:51ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-10-011310.3389/fmicb.2022.928317928317A pilot study to show that asymptomatic sexually transmitted infections alter the foreskin epithelial proteomeNyaradzo T. L. Chigorimbo-Murefu0Matthys Potgieter1Matthys Potgieter2Sonwabile Dzanibe3Zikhona Gabazana4Gershom Buri5Aditya Chawla6Bokani Nleya7Abraham J. Olivier8Rushil Harryparsad9Bridget Calder10Shaun Garnett11Lungile Maziya12David A. Lewis13David A. Lewis14Heather Jaspan15Heather Jaspan16Heather Jaspan17Doug Wilson18Jo-Ann S. Passmore19Nicola Mulder20Jonathan Blackburn21Linda-Gail Bekker22Clive M. Gray23Clive M. Gray24Divisions of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDivision of Computational Biology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDivision of Chemical and Systems Biology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDivision of Immunology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDivision of Computational Biology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDivision of Immunology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDivision of Immunology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDivision of Immunology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDivision of Immunology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDivisions of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDivision of Chemical and Systems Biology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDivision of Chemical and Systems Biology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDepartment of Medicine, Edendale Hospital, Pietermaritzburg, South AfricaWestern Sydney Sexual Health Centre, Western Sydney Local Health District, Parramatta, NSW, AustraliaWestmead Clinical School and Sydney Institute for Infectious Diseases, University of Sydney, Sydney, NSW, AustraliaDivision of Immunology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaSeattle Children’s Research Institute, Seattle, WA, United StatesDepartment of Global Health, University of Washington, Seattle, WA, United StatesDepartment of Medicine, Edendale Hospital, Pietermaritzburg, South AfricaDivisions of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDivision of Computational Biology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDivision of Chemical and Systems Biology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa0Desmond Tutu HIV Centre, Cape Town, South AfricaDivision of Immunology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa1Division of Molecular Biology and Human Genetics, Stellenbosch University, Cape Town, South AfricaThere is limited data on the role of asymptomatic STIs (aSTIs) on the risk of human immunodeficiency virus (HIV) acquisition in the male genital tract (MGT). The impact of foreskin removal on lowering HIV acquisition is well described, but molecular events leading to HIV acquisition are unclear. Here, in this pilot study, we show that asymptomatic urethral infection with Chlamydia trachomatis (CT) significantly impacts the foreskin proteome composition. We developed and optimized a shotgun liquid chromatography coupled tandem mass spectrometry (MS)-based proteomics approach and utilized this on foreskins collected at medical male circumcision (MMC) from 16 aSTI+ men and 10 age-matched STI- controls. We used a novel bioinformatic metaproteomic pipeline to detect differentially expressed (DE) proteins. Gene enrichment ontology analysis revealed proteins associated with inflammatory and immune activation function in both inner and outer foreskin from men with an aSTI. Neutrophil activation/degranulation and viral-evasion proteins were significantly enriched in foreskins from men with aSTI, whereas homotypic cell–cell adhesion proteins were enriched in foreskin tissue from men without an aSTI. Collectively, our data show that asymptomatic urethral sexually transmitted infections result in profound alterations in epithelial tissue that are associated with depletion of barrier integrity and immune activation.https://www.frontiersin.org/articles/10.3389/fmicb.2022.928317/fullasymptomatic sexually transmitted infectionforeskinforeskin proteomeHIV susceptibilitygene ontology enrichment analysis |
spellingShingle | Nyaradzo T. L. Chigorimbo-Murefu Matthys Potgieter Matthys Potgieter Sonwabile Dzanibe Zikhona Gabazana Gershom Buri Aditya Chawla Bokani Nleya Abraham J. Olivier Rushil Harryparsad Bridget Calder Shaun Garnett Lungile Maziya David A. Lewis David A. Lewis Heather Jaspan Heather Jaspan Heather Jaspan Doug Wilson Jo-Ann S. Passmore Nicola Mulder Jonathan Blackburn Linda-Gail Bekker Clive M. Gray Clive M. Gray A pilot study to show that asymptomatic sexually transmitted infections alter the foreskin epithelial proteome Frontiers in Microbiology asymptomatic sexually transmitted infection foreskin foreskin proteome HIV susceptibility gene ontology enrichment analysis |
title | A pilot study to show that asymptomatic sexually transmitted infections alter the foreskin epithelial proteome |
title_full | A pilot study to show that asymptomatic sexually transmitted infections alter the foreskin epithelial proteome |
title_fullStr | A pilot study to show that asymptomatic sexually transmitted infections alter the foreskin epithelial proteome |
title_full_unstemmed | A pilot study to show that asymptomatic sexually transmitted infections alter the foreskin epithelial proteome |
title_short | A pilot study to show that asymptomatic sexually transmitted infections alter the foreskin epithelial proteome |
title_sort | pilot study to show that asymptomatic sexually transmitted infections alter the foreskin epithelial proteome |
topic | asymptomatic sexually transmitted infection foreskin foreskin proteome HIV susceptibility gene ontology enrichment analysis |
url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.928317/full |
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