The mast cell tumor necrosis factor alpha response to FimH-expressing Escherichia coli is mediated by the glycosylphosphatidylinositol-anchored molecule CD48

Mast cells are well known for their harmful role in IgE-mediated hypersensi tivity reactions, but their physiological role remains a mystery. Several r ecent studies have reported that mast cells play a critical role in innate immunity in mice by releasing tumor necrosis factor alpha (TNF-alpha) to re cruit,neutrophils to sites of enterobacterial infection. In some cases, the mast cell TNF-alpha response was triggered when these cells directly bound FimH on the surface of Escherichia coli, We have identified CD48, a glycos ylphosphatidylinositol-anchored molecule, to be the complementary FimH-bind ing moiety in rodent mast cell membrane fractions. We showed that (i) pretr eatment of mast cell membranes with antibodies to CD48 or phospholipase C i nhibited binding of FimH(+) E. coli, (ii) FimH(+) E. coli but not a FimH(-) derivative bound isolated CD48 in a mannose-inhibitable manner, (iii) bind ing of FimH(+) bacteria to Chinese hamster ovary (CHO) cells was markedly i ncreased when these cells were transfected with CD48 cDNA, and (iv) antibod ies to CD48 specifically blocked the mast cell TNF-alpha response to FimH() E. coli. Thus, CD48 is a functionally relevant microbial receptor on mast cells that plays a role in triggering inflammation.