Basophils are rapidly mobilized following initial aeroallergen encounter in naïve mice and provide a priming source of IL-4 in adaptive immune responses

Abstract

Chronic aeroallergen inhalation elicits the expansion of IL-4-producing Th2 cells and the production of IgE antibodies. In sensitized subjects, who have established IgE and Th2 responses, re-exposure to allergen leads to rapid recruitment of basophils, which are thought to be important effectors of late phase allergic reactions. Several investigations of responses to parasites and injected antigens have identified an additional role for basophils as innate immune effectors during initial antigen encounter in immunologically naïve hosts. These cells constitutively express IL-4 and promote Th2 polarized adaptive responses to such antigens. Their early recruitment and modulation of cellular immune responses to natural inhaled allergens in the airways has been scarcely investigated. In this study, basophils were enumerated in lung tissue, blood and spleen from BALB/c mice in the first days after inhalation of an aqueous extract of the allergen, Aspergillus fumigatus (Af). Af inhalation induced rapid increases in basophil numbers in the lung, blood and spleen. This was Rag-1-, MyD88- and IL-3-independent. The basophils expressed abundant IL-4. Their depletion during Af sensitization resulted in an attenuated induction of both IL-4 producing Th lymphocytes and specific IgE and IgG1 responses to an inhaled protein antigen, ovalbumin, which was co-administered. Our results suggest that basophils are rapidly recruited to the airways of naïve mice following initial fungal allergen exposure, produce IL-4 and influence the development of the adaptive immune response.