SAA1 sees PAMP in the mite

Abstract

Immunology If you wake up with streaming eyes and nose, it could be that you are allergic to the house dust mite. The molecular mechanisms through which the molecular patterns of such organisms initiate allergic responses is poorly understood. Smole et al . report that the highly conserved acute-phase protein serum amyloid A1 (SAA1) acts as a soluble pattern recognition receptor for mite fatty acid–binding allergens Der p 13 and Blo t 13. These allergens disrupt lipid-stabilized SAA1 hexamers to adopt monomeric states that preferentially bind formyl peptide receptor 2 (FPR2). Activation of FPR2 in turn activates epithelial cell release of the potent allergy-inducing cytokine interleukin-33. This work opens new routes for investigating treatment of allergic disease while potentially offering insights into the pathogenesis of other SAA1- associated disorders such as atherosclerosis and Alzheimer's disease. Nat. Immunol. 21 , 756 (2020).