Helicobacter pylori binds to CD74 on gastric epithelial cells and stimulates interleukin-8 production.
The pathogenesis associated with Helicobacter pylori infection requires consistent contact with the gastric epithelium. Although several cell surface receptors have been suggested to play a role in adhesion, the bacterium-host interactions that elicit host responses are not well defined. This study investigated the interaction of H. pylori with the class II major histocompatibility complex (MHC)-associated invariant chain (Ii; CD74), which was found to be highly expressed by gastric epithelial cells. Bacterial binding was increased when CD74 surface expression was increased by gamma interferon (IFN-gamma) treatment or by fibroblast cells transfected with CD74, while binding was decreased by CD74 blocking antibodies, enzyme cleavage of CD74, and CD74-coated bacteria. H. pylori was also shown to bind directly to affinity-purified CD74 in the absence of class II MHC. Cross-linking of CD74 and the engagement of CD74 were verified to stimulate IL-8 production by unrelated cell lines expressing CD74 in the absence of class II MHC. Increased CD74 expression by cells increased IL-8 production in response to H. pylori, and agents that block CD74 decreased these responses. The binding of H. pylori to CD74 presents a novel insight into an initial interaction of H. pylori with the gastric epithelium that leads to upregulation of inflammatory responses.
Beswick
Ellen J
EJ
Children's Hospital, Room 2.300, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USA.
Bland
David A
DA
Suarez
Giovanni
G
Barrera
Carlos A
CA
Fan
Xuejung
X
Reyes
Victor E
VE
D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D001422:Bacterial Adhesion; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology*; D005347:Fibroblasts; D005753:Gastric Mucosa / Q000166:cytology / Q000382:microbiology*; D016480:Helicobacter pylori / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D014162:Transfection; D015854:Up-Regulation
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D016209:Interleukin-8; C045084:invariant chain