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 hypersensitivity reactions, but their physiological role remains a mystery. Several recent studies have reported that mast cells play a critical role in innate immunity in mice by releasing tumor necrosis factor alpha (TNF-alpha) to recruit 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 glycosylphosphatidylinositol-anchored molecule, to be the complementary FimH-binding moiety in rodent mast cell membrane fractions. We showed that (i) pretreatment of mast cell membranes with antibodies to CD48 or phospholipase C inhibited binding of FimH+ E. coli, (ii) FimH+ E. coli but not a FimH- derivative bound isolated CD48 in a mannose-inhibitable manner, (iii) binding of FimH+ bacteria to Chinese hamster ovary (CHO) cells was markedly increased when these cells were transfected with CD48 cDNA, and (iv) antibodies 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.
Department of Pathology and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
R
R
Malaviya
Z
Z
Gao
K
K
Thankavel
P A
PA
van der Merwe
S N
SN
Abraham
D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D018830:Adhesins, Escherichia coli; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D001422:Bacterial Adhesion; D000071178:CD48 Antigen; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D004926:Escherichia coli; D036781:Fimbriae Proteins; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism
D018829:Adhesins, Bacterial; D018830:Adhesins, Escherichia coli; D015703:Antigens, CD; D000071178:CD48 Antigen; C000604066:Cd48 protein, mouse; D017261:Glycosylphosphatidylinositols; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C058769:fimH protein, E coli; D036781:Fimbriae Proteins; D010738:Type C Phospholipases