Cargando…
Kinetics of Myeloid Dendritic Cell Trafficking and Activation: Impact on Progressive, Nonprogressive and Controlled SIV Infections
We assessed the role of myeloid dendritic cells (mDCs) in the outcome of SIV infection by comparing and contrasting their frequency, mobilization, phenotype, cytokine production and apoptosis in pathogenic (pigtailed macaques, PTMs), nonpathogenic (African green monkeys, AGMs) and controlled (rhesus...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3789723/ https://www.ncbi.nlm.nih.gov/pubmed/24098110 http://dx.doi.org/10.1371/journal.ppat.1003600 |
_version_ | 1782286484401815552 |
---|---|
author | Wijewardana, Viskam Kristoff, Jan Xu, Cuiling Ma, Dongzhu Haret-Richter, George Stock, Jennifer L. Policicchio, Benjamin B. Mobley, Adam D. Nusbaum, Rebecca Aamer, Hadega Trichel, Anita Ribeiro, Ruy M. Apetrei, Cristian Pandrea, Ivona |
author_facet | Wijewardana, Viskam Kristoff, Jan Xu, Cuiling Ma, Dongzhu Haret-Richter, George Stock, Jennifer L. Policicchio, Benjamin B. Mobley, Adam D. Nusbaum, Rebecca Aamer, Hadega Trichel, Anita Ribeiro, Ruy M. Apetrei, Cristian Pandrea, Ivona |
author_sort | Wijewardana, Viskam |
collection | PubMed |
description | We assessed the role of myeloid dendritic cells (mDCs) in the outcome of SIV infection by comparing and contrasting their frequency, mobilization, phenotype, cytokine production and apoptosis in pathogenic (pigtailed macaques, PTMs), nonpathogenic (African green monkeys, AGMs) and controlled (rhesus macaques, RMs) SIVagmSab infection. Through the identification of recently replicating cells, we demonstrated that mDC mobilization from the bone marrow occurred in all species postinfection, being most prominent in RMs. Circulating mDCs were depleted with disease progression in PTMs, recovered to baseline values after the viral peak in AGMs, and significantly increased at the time of virus control in RMs. Rapid disease progression in PTMs was associated with low baseline levels and incomplete recovery of circulating mDCs during chronic infection. mDC recruitment to the intestine occurred in all pathogenic scenarios, but loss of mucosal mDCs was associated only with progressive infection. Sustained mDC immune activation occurred throughout infection in PTMs and was associated with increased bystander apoptosis in blood and intestine. Conversely, mDC activation occurred only during acute infection in nonprogressive and controlled infections. Postinfection, circulating mDCs rapidly became unresponsive to TLR7/8 stimulation in all species. Yet, stimulation with LPS, a bacterial product translocated in circulation only in SIV-infected PTMs, induced mDC hyperactivation, apoptosis and excessive production of proinflammatory cytokines. After infection, spontaneous production of proinflammatory cytokines by mucosal mDCs increased only in progressor PTMs. We thus propose that mDCs promote tolerance to SIV in the biological systems that lack intestinal dysfunction. In progressive infections, mDC loss and excessive activation of residual mDCs by SIV and additional stimuli, such as translocated microbial products, enhance generalized immune activation and inflammation. Our results thus provide a mechanistic basis for the role of mDCs in the pathogenesis of AIDS and elucidate the causes of mDC loss during progressive HIV/SIV infections. |
format | Online Article Text |
id | pubmed-3789723 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37897232013-10-04 Kinetics of Myeloid Dendritic Cell Trafficking and Activation: Impact on Progressive, Nonprogressive and Controlled SIV Infections Wijewardana, Viskam Kristoff, Jan Xu, Cuiling Ma, Dongzhu Haret-Richter, George Stock, Jennifer L. Policicchio, Benjamin B. Mobley, Adam D. Nusbaum, Rebecca Aamer, Hadega Trichel, Anita Ribeiro, Ruy M. Apetrei, Cristian Pandrea, Ivona PLoS Pathog Research Article We assessed the role of myeloid dendritic cells (mDCs) in the outcome of SIV infection by comparing and contrasting their frequency, mobilization, phenotype, cytokine production and apoptosis in pathogenic (pigtailed macaques, PTMs), nonpathogenic (African green monkeys, AGMs) and controlled (rhesus macaques, RMs) SIVagmSab infection. Through the identification of recently replicating cells, we demonstrated that mDC mobilization from the bone marrow occurred in all species postinfection, being most prominent in RMs. Circulating mDCs were depleted with disease progression in PTMs, recovered to baseline values after the viral peak in AGMs, and significantly increased at the time of virus control in RMs. Rapid disease progression in PTMs was associated with low baseline levels and incomplete recovery of circulating mDCs during chronic infection. mDC recruitment to the intestine occurred in all pathogenic scenarios, but loss of mucosal mDCs was associated only with progressive infection. Sustained mDC immune activation occurred throughout infection in PTMs and was associated with increased bystander apoptosis in blood and intestine. Conversely, mDC activation occurred only during acute infection in nonprogressive and controlled infections. Postinfection, circulating mDCs rapidly became unresponsive to TLR7/8 stimulation in all species. Yet, stimulation with LPS, a bacterial product translocated in circulation only in SIV-infected PTMs, induced mDC hyperactivation, apoptosis and excessive production of proinflammatory cytokines. After infection, spontaneous production of proinflammatory cytokines by mucosal mDCs increased only in progressor PTMs. We thus propose that mDCs promote tolerance to SIV in the biological systems that lack intestinal dysfunction. In progressive infections, mDC loss and excessive activation of residual mDCs by SIV and additional stimuli, such as translocated microbial products, enhance generalized immune activation and inflammation. Our results thus provide a mechanistic basis for the role of mDCs in the pathogenesis of AIDS and elucidate the causes of mDC loss during progressive HIV/SIV infections. Public Library of Science 2013-10-03 /pmc/articles/PMC3789723/ /pubmed/24098110 http://dx.doi.org/10.1371/journal.ppat.1003600 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Wijewardana, Viskam Kristoff, Jan Xu, Cuiling Ma, Dongzhu Haret-Richter, George Stock, Jennifer L. Policicchio, Benjamin B. Mobley, Adam D. Nusbaum, Rebecca Aamer, Hadega Trichel, Anita Ribeiro, Ruy M. Apetrei, Cristian Pandrea, Ivona Kinetics of Myeloid Dendritic Cell Trafficking and Activation: Impact on Progressive, Nonprogressive and Controlled SIV Infections |
title | Kinetics of Myeloid Dendritic Cell Trafficking and Activation: Impact on Progressive, Nonprogressive and Controlled SIV Infections |
title_full | Kinetics of Myeloid Dendritic Cell Trafficking and Activation: Impact on Progressive, Nonprogressive and Controlled SIV Infections |
title_fullStr | Kinetics of Myeloid Dendritic Cell Trafficking and Activation: Impact on Progressive, Nonprogressive and Controlled SIV Infections |
title_full_unstemmed | Kinetics of Myeloid Dendritic Cell Trafficking and Activation: Impact on Progressive, Nonprogressive and Controlled SIV Infections |
title_short | Kinetics of Myeloid Dendritic Cell Trafficking and Activation: Impact on Progressive, Nonprogressive and Controlled SIV Infections |
title_sort | kinetics of myeloid dendritic cell trafficking and activation: impact on progressive, nonprogressive and controlled siv infections |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3789723/ https://www.ncbi.nlm.nih.gov/pubmed/24098110 http://dx.doi.org/10.1371/journal.ppat.1003600 |
work_keys_str_mv | AT wijewardanaviskam kineticsofmyeloiddendriticcelltraffickingandactivationimpactonprogressivenonprogressiveandcontrolledsivinfections AT kristoffjan kineticsofmyeloiddendriticcelltraffickingandactivationimpactonprogressivenonprogressiveandcontrolledsivinfections AT xucuiling kineticsofmyeloiddendriticcelltraffickingandactivationimpactonprogressivenonprogressiveandcontrolledsivinfections AT madongzhu kineticsofmyeloiddendriticcelltraffickingandactivationimpactonprogressivenonprogressiveandcontrolledsivinfections AT haretrichtergeorge kineticsofmyeloiddendriticcelltraffickingandactivationimpactonprogressivenonprogressiveandcontrolledsivinfections AT stockjenniferl kineticsofmyeloiddendriticcelltraffickingandactivationimpactonprogressivenonprogressiveandcontrolledsivinfections AT policicchiobenjaminb kineticsofmyeloiddendriticcelltraffickingandactivationimpactonprogressivenonprogressiveandcontrolledsivinfections AT mobleyadamd kineticsofmyeloiddendriticcelltraffickingandactivationimpactonprogressivenonprogressiveandcontrolledsivinfections AT nusbaumrebecca kineticsofmyeloiddendriticcelltraffickingandactivationimpactonprogressivenonprogressiveandcontrolledsivinfections AT aamerhadega kineticsofmyeloiddendriticcelltraffickingandactivationimpactonprogressivenonprogressiveandcontrolledsivinfections AT trichelanita kineticsofmyeloiddendriticcelltraffickingandactivationimpactonprogressivenonprogressiveandcontrolledsivinfections AT ribeiroruym kineticsofmyeloiddendriticcelltraffickingandactivationimpactonprogressivenonprogressiveandcontrolledsivinfections AT apetreicristian kineticsofmyeloiddendriticcelltraffickingandactivationimpactonprogressivenonprogressiveandcontrolledsivinfections AT pandreaivona kineticsofmyeloiddendriticcelltraffickingandactivationimpactonprogressivenonprogressiveandcontrolledsivinfections |