Cargando…
Differential response of BDCA-1(+) and BDCA-3(+) myeloid dendritic cells to respiratory syncytial virus infection
BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of respiratory infections in children, elderly, and immunocompromised individuals. Severe infection is associated with short- and long-term morbidity including pneumonia, recurrent wheezing, and abnormal pulmonary function, and sever...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708742/ https://www.ncbi.nlm.nih.gov/pubmed/23829893 http://dx.doi.org/10.1186/1465-9921-14-71 |
_version_ | 1782276649830580224 |
---|---|
author | Gupta, Meera R Kolli, Deepthi Garofalo, Roberto P |
author_facet | Gupta, Meera R Kolli, Deepthi Garofalo, Roberto P |
author_sort | Gupta, Meera R |
collection | PubMed |
description | BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of respiratory infections in children, elderly, and immunocompromised individuals. Severe infection is associated with short- and long-term morbidity including pneumonia, recurrent wheezing, and abnormal pulmonary function, and several lines of evidence indicate that impaired adaptive immune responses during infection are critical in the pathophysiology of RSV-mediated disease. Myeloid Dendritic cells (mDCs) play a pivotal role in shaping antiviral immune responses in the respiratory tract; however, few studies have examined the interactions between RSV and individual mDC subsets. In this study, we examined the effect of RSV on the functional response of primary mDC subsets (BDCA-1(+) and BDCA-3(+)) isolated from peripheral blood. METHODS: BDCA-1(+) and BDCA-3(+) mDCs were isolated from the peripheral blood of healthy adults using FACS sorting. Donor-matched BDCA-1(+) and BDCA-3(+) mDCs were infected with RSV at a multiplicity of infection (MOI) of 5 for 40 hours. After infection, cells were analyzed for the expression of costimulatory molecules (CD86, CD80, and PD-L1), cytokine production, and the ability to stimulate allogenic CD4(+) T cell proliferation. RESULTS: Both BDCA-1(+) and BDCA-3(+) mDCs were susceptible to infection with RSV and demonstrated enhanced expression of CD86, and the inhibitory costimulatory molecules CD80 and PD-L1. Compared to BDCA-3(+) mDCs, RSV-infected BDCA-1(+) mDC produced a profile of cytokines and chemokines predominantly associated with pro-inflammatory responses (IL-1β, IL-6, IL-12, MIP-1α, and TNF-α), and both BDCA-1(+) and BDCA-3(+) mDCs were found to produce IL-10. Compared to uninfected mDCs, RSV-infected BDCA-1(+) and BDCA-3(+) mDCs demonstrated a reduced capacity to stimulate T cell proliferation. CONCLUSIONS: RSV infection induces a distinct pattern of costimulatory molecule expression and cytokine production by BDCA-1(+) and BDCA-3(+) mDCs, and impairs their ability to stimulate T cell proliferation. The differential expression of CD86 and pro-inflammatory cytokines by highly purified mDC subsets in response to RSV provides further evidence that BDCA-1(+) and BDCA-3(+) mDCs have distinct roles in coordinating the host immune response during RSV infection. Findings of differential expression of PD-L1 and IL-10 by infected mDCs, suggests possible mechanisms by which RSV is able to impair adaptive immune responses. |
format | Online Article Text |
id | pubmed-3708742 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-37087422013-07-12 Differential response of BDCA-1(+) and BDCA-3(+) myeloid dendritic cells to respiratory syncytial virus infection Gupta, Meera R Kolli, Deepthi Garofalo, Roberto P Respir Res Research BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of respiratory infections in children, elderly, and immunocompromised individuals. Severe infection is associated with short- and long-term morbidity including pneumonia, recurrent wheezing, and abnormal pulmonary function, and several lines of evidence indicate that impaired adaptive immune responses during infection are critical in the pathophysiology of RSV-mediated disease. Myeloid Dendritic cells (mDCs) play a pivotal role in shaping antiviral immune responses in the respiratory tract; however, few studies have examined the interactions between RSV and individual mDC subsets. In this study, we examined the effect of RSV on the functional response of primary mDC subsets (BDCA-1(+) and BDCA-3(+)) isolated from peripheral blood. METHODS: BDCA-1(+) and BDCA-3(+) mDCs were isolated from the peripheral blood of healthy adults using FACS sorting. Donor-matched BDCA-1(+) and BDCA-3(+) mDCs were infected with RSV at a multiplicity of infection (MOI) of 5 for 40 hours. After infection, cells were analyzed for the expression of costimulatory molecules (CD86, CD80, and PD-L1), cytokine production, and the ability to stimulate allogenic CD4(+) T cell proliferation. RESULTS: Both BDCA-1(+) and BDCA-3(+) mDCs were susceptible to infection with RSV and demonstrated enhanced expression of CD86, and the inhibitory costimulatory molecules CD80 and PD-L1. Compared to BDCA-3(+) mDCs, RSV-infected BDCA-1(+) mDC produced a profile of cytokines and chemokines predominantly associated with pro-inflammatory responses (IL-1β, IL-6, IL-12, MIP-1α, and TNF-α), and both BDCA-1(+) and BDCA-3(+) mDCs were found to produce IL-10. Compared to uninfected mDCs, RSV-infected BDCA-1(+) and BDCA-3(+) mDCs demonstrated a reduced capacity to stimulate T cell proliferation. CONCLUSIONS: RSV infection induces a distinct pattern of costimulatory molecule expression and cytokine production by BDCA-1(+) and BDCA-3(+) mDCs, and impairs their ability to stimulate T cell proliferation. The differential expression of CD86 and pro-inflammatory cytokines by highly purified mDC subsets in response to RSV provides further evidence that BDCA-1(+) and BDCA-3(+) mDCs have distinct roles in coordinating the host immune response during RSV infection. Findings of differential expression of PD-L1 and IL-10 by infected mDCs, suggests possible mechanisms by which RSV is able to impair adaptive immune responses. BioMed Central 2013 2013-07-05 /pmc/articles/PMC3708742/ /pubmed/23829893 http://dx.doi.org/10.1186/1465-9921-14-71 Text en Copyright © 2013 Gupta et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Gupta, Meera R Kolli, Deepthi Garofalo, Roberto P Differential response of BDCA-1(+) and BDCA-3(+) myeloid dendritic cells to respiratory syncytial virus infection |
title | Differential response of BDCA-1(+) and BDCA-3(+) myeloid dendritic cells to respiratory syncytial virus infection |
title_full | Differential response of BDCA-1(+) and BDCA-3(+) myeloid dendritic cells to respiratory syncytial virus infection |
title_fullStr | Differential response of BDCA-1(+) and BDCA-3(+) myeloid dendritic cells to respiratory syncytial virus infection |
title_full_unstemmed | Differential response of BDCA-1(+) and BDCA-3(+) myeloid dendritic cells to respiratory syncytial virus infection |
title_short | Differential response of BDCA-1(+) and BDCA-3(+) myeloid dendritic cells to respiratory syncytial virus infection |
title_sort | differential response of bdca-1(+) and bdca-3(+) myeloid dendritic cells to respiratory syncytial virus infection |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708742/ https://www.ncbi.nlm.nih.gov/pubmed/23829893 http://dx.doi.org/10.1186/1465-9921-14-71 |
work_keys_str_mv | AT guptameerar differentialresponseofbdca1andbdca3myeloiddendriticcellstorespiratorysyncytialvirusinfection AT kollideepthi differentialresponseofbdca1andbdca3myeloiddendriticcellstorespiratorysyncytialvirusinfection AT garofalorobertop differentialresponseofbdca1andbdca3myeloiddendriticcellstorespiratorysyncytialvirusinfection |