Modulation of female genital tract-derived dendritic cell migration and activation in response to inflammatory cytokines and toll-like receptor agonists

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dc.contributor.authorShey, Muki Sen_ZA
dc.contributor.authorMaharaj, Nirenen_ZA
dc.contributor.authorArchary, Dersereeen_ZA
dc.contributor.authorNgcapu, Sinayeen_ZA
dc.contributor.authorGarrett, Nigelen_ZA
dc.contributor.authorKarim, Salim Abdoolen_ZA
dc.contributor.authorPassmore, Jo-Ann Sen_ZA
dc.date.accessioned2016-10-31T07:38:08Z
dc.date.available2016-10-31T07:38:08Z
dc.date.issued2016en_ZA
dc.description.abstractHIV transmission across the genital mucosa is a major mode of new HIV infections in women. The probability of infection may be influenced by several factors including recruitment and activation of HIV target cells, such as dendritic cells (DCs) and cytokine production, associated with genital inflammation. We evaluated the role of inflammatory cytokines and TLR signaling in migration and activation of genital tract DCs in the human cervical explant model. Hysterectomy tissues from 10 HIV-negative and 7 HIV-positive donor women were separated into ecto- and endocervical explants, and incubated with inflammatory cytokines (TNF-α, IL-1β, IL-8, MIP-1β) or agonists for TLR4 (LPS), TLR2/1 (PAM3) and TLR7/8 (R848). Migration (frequency) and activation (HLA-DR expression) of myeloid and plasmacytoid DCs and Langerhans cells were measured by flow cytometry. We observed that cytokines, LPS and PAM3 induced activation of migrating myeloid and plasmacytoid DCs. LPS induced a 3.6 fold lower levels of migration of plasmacytoid DCs from HIV-infected women compared with HIV-uninfected women (median activation indices of 2.932 vs 0.833). There was however a 4.5 fold increase in migration of Langerhans cells in HIV-infected compared with HIV-uninfected women in response to cytokines (median activation indices of 3.539 vs 0.77). Only TLR agonists induced migration and activation of DCs from endocervical explants. Hormonal contraception use was associated with an increase in activation of DC subsets in the endo and ectocervical explants. We conclude that inflammatory signals in the female genital tract induced DC migration and activation, with possible important implications for HIV susceptibility of cervical tissues.en_ZA
dc.identifier.apacitationShey, M. S., Maharaj, N., Archary, D., Ngcapu, S., Garrett, N., Karim, S. A., & Passmore, J. S. (2016). Modulation of female genital tract-derived dendritic cell migration and activation in response to inflammatory cytokines and toll-like receptor agonists. <i>PLoS One</i>, http://hdl.handle.net/11427/22360en_ZA
dc.identifier.chicagocitationShey, Muki S, Niren Maharaj, Derseree Archary, Sinaye Ngcapu, Nigel Garrett, Salim Abdool Karim, and Jo-Ann S Passmore "Modulation of female genital tract-derived dendritic cell migration and activation in response to inflammatory cytokines and toll-like receptor agonists." <i>PLoS One</i> (2016) http://hdl.handle.net/11427/22360en_ZA
dc.identifier.citationShey, M. S., Maharaj, N., Archary, D., Ngcapu, S., Garrett, N., Karim, S. A., & Passmore, J. A. S. (2016). Modulation of female genital tract-derived dendritic cell migration and activation in response to inflammatory cytokines and toll-like receptor agonists. PloS one, 11(5), e0155668. doi:10.1371/journal.pone.0155668en_ZA
dc.identifier.ris TY - Journal Article AU - Shey, Muki S AU - Maharaj, Niren AU - Archary, Derseree AU - Ngcapu, Sinaye AU - Garrett, Nigel AU - Karim, Salim Abdool AU - Passmore, Jo-Ann S AB - HIV transmission across the genital mucosa is a major mode of new HIV infections in women. The probability of infection may be influenced by several factors including recruitment and activation of HIV target cells, such as dendritic cells (DCs) and cytokine production, associated with genital inflammation. We evaluated the role of inflammatory cytokines and TLR signaling in migration and activation of genital tract DCs in the human cervical explant model. Hysterectomy tissues from 10 HIV-negative and 7 HIV-positive donor women were separated into ecto- and endocervical explants, and incubated with inflammatory cytokines (TNF-α, IL-1β, IL-8, MIP-1β) or agonists for TLR4 (LPS), TLR2/1 (PAM3) and TLR7/8 (R848). Migration (frequency) and activation (HLA-DR expression) of myeloid and plasmacytoid DCs and Langerhans cells were measured by flow cytometry. We observed that cytokines, LPS and PAM3 induced activation of migrating myeloid and plasmacytoid DCs. LPS induced a 3.6 fold lower levels of migration of plasmacytoid DCs from HIV-infected women compared with HIV-uninfected women (median activation indices of 2.932 vs 0.833). There was however a 4.5 fold increase in migration of Langerhans cells in HIV-infected compared with HIV-uninfected women in response to cytokines (median activation indices of 3.539 vs 0.77). Only TLR agonists induced migration and activation of DCs from endocervical explants. Hormonal contraception use was associated with an increase in activation of DC subsets in the endo and ectocervical explants. We conclude that inflammatory signals in the female genital tract induced DC migration and activation, with possible important implications for HIV susceptibility of cervical tissues. DA - 2016 DB - OpenUCT DO - 10.1371/journal.pone.0155668 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2016 T1 - Modulation of female genital tract-derived dendritic cell migration and activation in response to inflammatory cytokines and toll-like receptor agonists TI - Modulation of female genital tract-derived dendritic cell migration and activation in response to inflammatory cytokines and toll-like receptor agonists UR - http://hdl.handle.net/11427/22360 ER - en_ZA
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0155668en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/22360
dc.identifier.vancouvercitationShey MS, Maharaj N, Archary D, Ngcapu S, Garrett N, Karim SA, et al. Modulation of female genital tract-derived dendritic cell migration and activation in response to inflammatory cytokines and toll-like receptor agonists. PLoS One. 2016; http://hdl.handle.net/11427/22360.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2016 Shey et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherCytokinesen_ZA
dc.subject.otherHIVen_ZA
dc.subject.otherInflammationen_ZA
dc.subject.otherHIV infectionsen_ZA
dc.subject.otherBlooden_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherImmune responseen_ZA
dc.subject.otherCell migrationen_ZA
dc.titleModulation of female genital tract-derived dendritic cell migration and activation in response to inflammatory cytokines and toll-like receptor agonistsen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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