Mgl2+ cDC2s coordinate fungal allergic airway type 2, but not type 17, inflammation in mice
Peter C. Cook, Sheila Brown, Emma L. Houlder, Julio Furlong-Silva, Daniel P. Conn, Stefano A. P. Colombo, Syed Murtuza Baker, Freya R. Svedberg, Gareth Howell, Margherita Bertuzzi, Louis Boon, Joanne E. Konkel, Christopher R. Thornton, Judith E. Allen, Andrew S. MacDonald
Abstract
Abstract Fungal spores are abundant in the environment and a major cause of asthma. Originally characterised as a type 2 inflammatory disease, allergic airway inflammation that underpins asthma can also involve type 17 inflammation, which can exacerbate disease causing failure of treatments tailored to inhibit type 2 factors. However, the mechanisms that determine the host response to fungi, which can trigger both type 2 and type 17 inflammation in allergic airway disease, remain unclear. Here we find that CD11c + DCs and CD4 + T cells are essential for development of both type 2 and type 17 airway inflammation in mice repeatedly exposed to inhaled spores. Single cell RNA-sequencing with further multi-parameter cytometry shows that allergic inflammation dramatically alters the proportion of numerous DC clusters in the lung, but that only two of these (Mgl2 + cDC2s and CCR7 + DCs) migrate to the dLNs. Targeted removal of several DC subsets shows that Mgl2 + cDC2 depletion reduces type 2, but not type 17, fungal allergic airway inflammation. These data highlight distinct DC subsets as potential therapeutic targets for the treatment of pulmonary fungal disease.