Crosstalk between the ά2Β1 integrin and c-met/HGF-R regulates innate immunity

Abstract

Data from several investigators suggest that the α2β 1 integrin, a receptor for collagens, laminins, decorin, E-cadherin, matrix metalloproteinase-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 α2β 1 integrin expression by peritoneal mast cells (PMCs). Ligation of the α2β 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 α2β 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 FcRγ, is required for early innate immune response to Listeria. The binding of Listeria's Internalin B (InIB) to hepatocyte growth factor receptor (HGF-R)/cmet provides the costimulatory function required for PMC activation. Either HGF or Listeria InIB bound to c-met and either C1q or type I collagen bound to α2β 1 integrin stimulates PMC activation. These findings suggest that crosstalk between c-met and the α2β 1 integrin may contribute to mast-cell activation in autoimmune and inflammatory disorders.© 2008 by The American Society of Hematology.