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Activation of basophils by the double-stranded RNA poly(A:U) exacerbates allergic inflammation

Authors


  • Edited by: Hans-Uwe Simon

Correspondence

Dr. Nathalie Thieblemont, CNRS UMR 8147, Paris Descartes University, Faculty of Medicine, Necker Hospital, 161 rue de Sèvres 75015 Paris, France.

Tel.: +33 1 44 49 53 88

Fax: +33 1 44 49 06 76

E-mail: nathalie.thieblemont@parisdescartes.fr

Abstract

Background

It is commonly acknowledged that asthma is exacerbated by viral infections. On the other hand, basophil infiltration of lung tissues has been evidenced postmortem in cases of fatal disease, raising the question of a possible link between these two observations.

Objectives

Herein, we addressed the relationship between asthma exacerbation by viral infection and basophil activation and expansion by investigating how stimulation with the dsRNA polyadenylic/polyuridylic acid [poly(A:U)] affected basophil activities and recruitment in an allergic airway inflammation model.

Methods

The effect of dsRNA on basophils was assessed by measuring the cytokine levels produced upon stimulation. We used an OVA-induced experimental model of allergic asthma. Airway hyperreactivity, recruitment of infiltrating cells, and cytokine production were determined in the lung of mice having received poly(A:U), as compared with untreated controls. The exacerbating effect of basophils was assessed both by adoptive transfer of poly(A:U)-treated basophils and by their in vivo depletion with Ba103 antibody.

Results

We found that in vitro treatment with poly(A:U) increased basophil functions by inducing TH2-type cytokine and histamine production, whereas in vivo treatment increased peripheral basophil recruitment. Furthermore, we provide the first demonstration for increased infiltration of basophils in the lung of mice suffering from airway inflammation. In this model, disease symptoms were clearly exacerbated upon adoptive transfer of basophils exposed to poly(A:U), relative to their unstimulated counterpart. Conversely, in vivo basophil depletion alleviated disease syndromes, thus validating the transfer data.

Conclusions

Our findings provide the first evidence for airway inflammation exacerbation by basophils following dsRNA stimulation.

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