Resident CD11b(+)Ly6C(-) lung dendritic cells are responsible for allergic airway sensitization to house dust mite in mice.

Claire Mesnil,Catherine M Sabatel,Marie Toussaint,Pierre-Vincent Drion,Christophe J Desmet,Fabrice Bureau,Pierre Lekeux,Thomas Marichal,Didier Cataldo

doi:10.1371/journal.pone.0053242

Abstract

Conventional dendritic cells (DCs) are considered to be the prime initiators of airway allergy. Yet, it remains unclear whether specific DC subsets are preferentially involved in allergic airway sensitization. Here, we systematically assessed the respective pro-allergic potential of individually sorted lung DC subsets isolated from house dust mite antigen (HDM)-treated donor mice, following transfer to naïve recipients. Transfer of lung CD11c+CD11b+ DCs, but not CD11c+CD11b−CD103+ DCs, was sufficient to prime airway allergy. The CD11c+CD11b+ DC subpopulation was composed of CD11c+CD11b+Ly6C+ inflammatory monocyte-derived cells, whose numbers increase in the lungs following HDM exposure, and of CD11c+CD11b+Ly6C− DCs, which remain stable. Counterintuitively, only CD11c+CD11b+Ly6C− DCs, and not CD11c+CD11b+Ly6C+ DCs, were able to convey antigen to the lymph nodes and induce adaptive T cell responses and subsequent airway allergy. Our results thus support that lung resident non-inflammatory CD11c+CD11b+Ly6C− DCs are the essential inducers of allergic airway sensitization to the common aeroallergen HDM in mice.

Highlights

Because it is key to the understanding, prevention and treatment of airway allergy, the question of how inhaled allergens lead to the activation of TH2 responses, the major orchestrators of allergy [1], is a subject of intense investigation
We reasoned that lung dendritic cells (DCs) of house dust mite antigens (HDM)-treated mice should be able to take up and process HDM antigens in vivo and, upon i.t. transfer to naıve recipient mice, to induce HDM-specific TH2 cell differentiation and airway allergy
We established a model of airway allergy based on the adoptive transfer of lung DCs isolated from donor mice exposed to the clinically relevant allergen HDM

Summary

Introduction

Because it is key to the understanding, prevention and treatment of airway allergy, the question of how inhaled allergens lead to the activation of TH2 responses, the major orchestrators of allergy [1], is a subject of intense investigation. Adoptive transfer experiments have been extensively used as an alternative to ablation approaches to support a role for DCs in allergic airway sensitization In these experiments, DCs isolated from the spleen of naıve mice [6] or derived in vitro from bone marrow progenitor cells [7] are loaded with antigen through in vitro culture, and transferred to naıve recipient mice, in which they induce antigen-specific TH2 responses

Methods

Results

Conclusion