Experimental rhinovirus infection induces an antiviral response in circulating B cells which is dysregulated in patients with asthma.

Oliver F Wirz, Kirstin Jansen, Pattraporn Satitsuksanoa, Willem van de Veen, Ge Tan, Milena Sokolowska, David Mirer, Barbara Stanić, Simon D Message, Tatiana Kebadze, Nicholas Glanville, Patrick Mallia, James E Gern, Nikolaos Papadopoulos, Cezmi A Akdis, Sebastian L Johnston, Kari Nadeau, Mübeccel Akdis

Journal: Allergy 2022;77(1):130-142

PMID: 34169553

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Abstract

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.

Address: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.; Christine Kühne - Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.; Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.; Functional Genomics Center Zürich, ETH Zürich/University of Zürich, Zürich, Switzerland.; National Heart and Lung Institute, Imperial College London, London, UK.; Department of Pediatrics, University of Wisconsin-Madison, Madison, USA.; Division of Infection, Immunity & Respiratory Medicine, The University of Manchester, Manchester, UK.; Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece.; Sean N. Parker Center for Allergy and Asthma Research, Department of Medicine, Stanford University, Palo Alto, California, USA.

DOI: 10.1111/all.14985

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MeSH Terms: Antiviral Agents, Asthma, Cytokines, Humans, Interferons, Picornaviridae Infections, Rhinovirus