Crosstalk between the α2β1 integrin and c-met/HGF-R regulates innate immunity

Data from several investigators suggest that the alpha integrin, a receptor for collagens, laminins, decorin, E-cadherin, matrix metal loprotei nase-1, endorepellin, and several viruses, is required for innate immunity and regulation of autoimmune/ allergic disorders. We demonstrated that the innate immune response to Listeria monocytogenes required alpha 2 beta 1 integrin expression by peritoneal mast cells (PMCs). Ligation of the alpha 2 beta 1 integrin by C1q contained in immune complexes comprised of Listeria and antibody was required for PMC activation in vitro and in vivo. However, ligation of the alpha 2 beta 1 integrin alone was insufficient to activate cytokine secretion, suggesting that one or more additional signals emanating from a coreceptor were required for PMC activation. Here, we demonstrate that C1q, but neither other complement proteins nor FcR gamma, is required for early innate immune response to Listeria. The binding of Listeria's Internalin B (InlB) to hepatocyte growth factor receptor (HGF-R)/c-met provides the costimulatory function required for PMC activation. Either HGF or Listeria InIB bound to c-met and either C1q or type 1 collagen bound to alpha 2 beta 1 integrin stimulates PMC activation. These findings suggest that crosstalk between c-met and the alpha 2 beta 1 integrin may contribute to mast-cell activation in autoimmune and inflammatory disorders.