Fungal chitin-binding glycoprotein induces Dectin-2-mediated allergic airway inflammation synergistically with chitin

Although chitin in fungal cell walls is associated with allergic airway inflammation, the precise mechanism underlying this association has yet to be elucidated. Here, we investigated the involvement of fungal chitin-binding protein and chitin in allergic airway inflammation. Recombinant Aspergillus fumigatus LdpA (rLdpA) expressed in Pichia pastoris was shown to be an O-linked glycoprotein containing terminal alpha-mannose residues recognized by the host C-type lectin receptor, Dectin-2. Chitin particles were shown to induce acute neutrophilic airway inflammation mediated release of interleukin-1 alpha (IL-1 alpha) associated with cell death. Furthermore, rLdpA-Dectin-2 interaction was shown to promote phagocytosis of rLdpA-chitin complex and activation of mouse bone marrow-derived dendritic cells (BMDCs). Moreover, we showed that rLdpA potently induced T helper 2 (Th2)-driven allergic airway inflammation synergistically with chitin, and Dectin-2 deficiency attenuated the rLdpA-chitin complex-induced immune response in vivo. In addition, we showed that serum LdpA-specific immunoglobulin levels were elevated in patients with pulmonary aspergillosis. Asthma is the most common chronic disease among children in many countries. Although its fundamental causes are not completely understood, the inhalation of allergens, including fungal spores is a known risk factor for the development of asthma. Recent studies have shown that sensitization to the filamentous fungus, Aspergillus fumigatus, is associated with exacerbation of allergic asthma and other pulmonary diseases. Although chitin in fungal cell walls is associated with allergic airway inflammation, the precise mechanism underlying this association has yet to be elucidated. In this study, we showed that A. fumigatus chitin-binding glycoprotein, LysM domain protein A (LdpA), synergistically induces Dectin-2-mediated Th2-driven airway inflammation with chitin. Therefore, this study provided new insights into fungal-induced allergic airway diseases.