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.author Shey, Muki S en_ZA
dc.contributor.author Maharaj, Niren en_ZA
dc.contributor.author Archary, Derseree en_ZA
dc.contributor.author Ngcapu, Sinaye en_ZA
dc.contributor.author Garrett, Nigel en_ZA
dc.contributor.author Karim, Salim Abdool en_ZA
dc.contributor.author Passmore, Jo-Ann S en_ZA
dc.date.accessioned 2016-10-31T07:38:08Z
dc.date.available 2016-10-31T07:38:08Z
dc.date.issued 2016 en_ZA
dc.identifier.citation Shey, 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.0155668 en_ZA
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0155668 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/22360
dc.description.abstract 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. en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This 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.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plosone en_ZA
dc.subject.other Cytokines en_ZA
dc.subject.other HIV en_ZA
dc.subject.other Inflammation en_ZA
dc.subject.other HIV infections en_ZA
dc.subject.other Blood en_ZA
dc.subject.other T cells en_ZA
dc.subject.other Immune response en_ZA
dc.subject.other Cell migration en_ZA
dc.title Modulation of female genital tract-derived dendritic cell migration and activation in response to inflammatory cytokines and toll-like receptor agonists en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2016 Shey et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Institute of Infectious Disease and Molecular Medicine en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Shey, 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/11427/22360 en_ZA
dc.identifier.chicagocitation Shey, 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/11427/22360 en_ZA
dc.identifier.vancouvercitation Shey 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.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


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This 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. Except where otherwise noted, this item's license is described as This 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.