Novel collectin/C1q receptor mediates mast cell activation and innate immunity

Mast cells play a critical role in innate immunity, allergy, and autoimmune diseases. The receptor/ligand interactions that mediate mast cell activation are poorly defined. The alpha(2)beta(1) integrin, a receptor for collagens, laminins, decorin, E-cadherin, matrix metalloproteinase-1 (MMP-1), endorepellin, and several viruses, has been implicated in normal developmental, inflammatory, and oncogenic processes. We recently reported that alpha(2) integrin subunit-deficient mice exhibited markedly diminished neutrophil and IL-6 responses during Listeria monocytogenes- and zymosan-induced peritonitis. Peritoneal mast cells require alpha(2)beta(1) integrin expression for activation in response to pathogens, yet the ligand and molecular mechanisms by which the alpha(2)beta(1) integrin induces activation and cytokine secretion remain unknown. We now report that the alpha(2)beta(1) integrin is a novel receptor for multiple collectins and the C1q complement protein. We demonstrate that the alpha(2)beta(1) integrin provides a costimulatory function required for mast cell activation and cytokine secretion. This finding suggests that the alpha(2)beta(1) integrin is not only important for innate immunity but may serve as a critical target for the regulation of autoimmune/allergic disorders.