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Experimental rhinovirus infection induces an antiviral response in circulating B cells which is dysregulated in patients with asthma
BACKGROUND: Rhinoviruses are the predominant cause of respiratory viral infections and are strongly associated with asthma exacerbations. While humoral immunity plays an important role during virus infections, cellular aspects of this response are less well understood. Here, we investigated the anti...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138744/ https://www.ncbi.nlm.nih.gov/pubmed/34169553 http://dx.doi.org/10.1111/all.14985 |
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author | Wirz, Oliver F. Jansen, Kirstin Satitsuksanoa, Pattraporn van de Veen, Willem Tan, Ge Sokolowska, Milena Mirer, David Stanić, Barbara Message, Simon D. Kebadze, Tatiana Glanville, Nicholas Mallia, Patrick Gern, James E. Papadopoulos, Nikolaos Akdis, Cezmi A. Johnston, Sebastian L. Nadeau, Kari Akdis, Mübeccel |
author_facet | Wirz, Oliver F. Jansen, Kirstin Satitsuksanoa, Pattraporn van de Veen, Willem Tan, Ge Sokolowska, Milena Mirer, David Stanić, Barbara Message, Simon D. Kebadze, Tatiana Glanville, Nicholas Mallia, Patrick Gern, James E. Papadopoulos, Nikolaos Akdis, Cezmi A. Johnston, Sebastian L. Nadeau, Kari Akdis, Mübeccel |
author_sort | Wirz, Oliver F. |
collection | PubMed |
description | BACKGROUND: Rhinoviruses are the predominant cause of respiratory viral infections and are strongly associated with asthma exacerbations. While humoral immunity plays an important role during virus infections, cellular aspects of this response are less well understood. Here, we investigated the antiviral response of circulating B cells upon experimental rhinovirus infection in healthy individuals and asthma patients. METHODS: We purified B cells from experimentally infected healthy individuals and patients with asthma and subjected them to total RNA‐sequencing. Rhinovirus‐derived RNA was measured in isolated B cells using a highly sensitive PCR. B cells were stimulated with rhinovirus in vitro to further study gene expression, expression of antiviral proteins and B‐cell differentiation in response rhinovirus stimulation. Protein expression of pro‐inflammatory cytokines in response to rhinovirus was assessed using a proximity extension assay. RESULTS: B cells isolated from experimentally infected subjects exhibited an antiviral gene profile linked to IFN‐alpha, carried viral RNA in vivo and were transiently infected by rhinovirus in vitro. B cells rapidly differentiated into plasmablasts upon rhinovirus stimulation. While B cells lacked expression of interferons in response to rhinovirus exposure, co‐stimulation with rhinovirus and IFN‐alpha upregulated pro‐inflammatory cytokine expression suggesting a potential new function of B cells during virus infections. Asthma patients showed extensive upregulation and dysregulation of antiviral gene expression. CONCLUSION: These findings add to the understanding of systemic effects of rhinovirus infections on B‐cell responses in the periphery, show potential dysregulation in patients with asthma and might also have implications during infection with other respiratory viruses. |
format | Online Article Text |
id | pubmed-10138744 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101387442023-04-28 Experimental rhinovirus infection induces an antiviral response in circulating B cells which is dysregulated in patients with asthma Wirz, Oliver F. Jansen, Kirstin Satitsuksanoa, Pattraporn van de Veen, Willem Tan, Ge Sokolowska, Milena Mirer, David Stanić, Barbara Message, Simon D. Kebadze, Tatiana Glanville, Nicholas Mallia, Patrick Gern, James E. Papadopoulos, Nikolaos Akdis, Cezmi A. Johnston, Sebastian L. Nadeau, Kari Akdis, Mübeccel Allergy ORIGINAL ARTICLES BACKGROUND: Rhinoviruses are the predominant cause of respiratory viral infections and are strongly associated with asthma exacerbations. While humoral immunity plays an important role during virus infections, cellular aspects of this response are less well understood. Here, we investigated the antiviral response of circulating B cells upon experimental rhinovirus infection in healthy individuals and asthma patients. METHODS: We purified B cells from experimentally infected healthy individuals and patients with asthma and subjected them to total RNA‐sequencing. Rhinovirus‐derived RNA was measured in isolated B cells using a highly sensitive PCR. B cells were stimulated with rhinovirus in vitro to further study gene expression, expression of antiviral proteins and B‐cell differentiation in response rhinovirus stimulation. Protein expression of pro‐inflammatory cytokines in response to rhinovirus was assessed using a proximity extension assay. RESULTS: B cells isolated from experimentally infected subjects exhibited an antiviral gene profile linked to IFN‐alpha, carried viral RNA in vivo and were transiently infected by rhinovirus in vitro. B cells rapidly differentiated into plasmablasts upon rhinovirus stimulation. While B cells lacked expression of interferons in response to rhinovirus exposure, co‐stimulation with rhinovirus and IFN‐alpha upregulated pro‐inflammatory cytokine expression suggesting a potential new function of B cells during virus infections. Asthma patients showed extensive upregulation and dysregulation of antiviral gene expression. CONCLUSION: These findings add to the understanding of systemic effects of rhinovirus infections on B‐cell responses in the periphery, show potential dysregulation in patients with asthma and might also have implications during infection with other respiratory viruses. John Wiley and Sons Inc. 2021-07-16 2022-01 /pmc/articles/PMC10138744/ /pubmed/34169553 http://dx.doi.org/10.1111/all.14985 Text en © 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | ORIGINAL ARTICLES Wirz, Oliver F. Jansen, Kirstin Satitsuksanoa, Pattraporn van de Veen, Willem Tan, Ge Sokolowska, Milena Mirer, David Stanić, Barbara Message, Simon D. Kebadze, Tatiana Glanville, Nicholas Mallia, Patrick Gern, James E. Papadopoulos, Nikolaos Akdis, Cezmi A. Johnston, Sebastian L. Nadeau, Kari Akdis, Mübeccel Experimental rhinovirus infection induces an antiviral response in circulating B cells which is dysregulated in patients with asthma |
title | Experimental rhinovirus infection induces an antiviral response in circulating B cells which is dysregulated in patients with asthma |
title_full | Experimental rhinovirus infection induces an antiviral response in circulating B cells which is dysregulated in patients with asthma |
title_fullStr | Experimental rhinovirus infection induces an antiviral response in circulating B cells which is dysregulated in patients with asthma |
title_full_unstemmed | Experimental rhinovirus infection induces an antiviral response in circulating B cells which is dysregulated in patients with asthma |
title_short | Experimental rhinovirus infection induces an antiviral response in circulating B cells which is dysregulated in patients with asthma |
title_sort | experimental rhinovirus infection induces an antiviral response in circulating b cells which is dysregulated in patients with asthma |
topic | ORIGINAL ARTICLES |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138744/ https://www.ncbi.nlm.nih.gov/pubmed/34169553 http://dx.doi.org/10.1111/all.14985 |
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