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Infection and Immunity, May 2005, p. 2736-2743, Vol. 73, No. 5
0019-9567/05/$08.00+0 doi:10.1128/IAI.73.5.2736-2743.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Helicobacter pylori Binds to CD74 on Gastric Epithelial Cells and Stimulates Interleukin-8 Production
Ellen J. Beswick,1
David A. Bland,2
Giovanni Suarez,1
Carlos A. Barrera,3
Xuejung Fan,1 and
Victor E. Reyes1,2*
Departments of Pediatrics,1
Pathology,3
Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 775552
Received 13 October 2004/
Returned for modification 29 November 2004/
Accepted 21 December 2004
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-
) 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.
* Corresponding author. Mailing address: Children's Hospital, Room 2.300, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555. Phone: (409) 772-3897. Fax: (409) 772-1761. E-mail:
vreyes{at}utmb.edu.
Editor: J. B. Bliska
Infection and Immunity, May 2005, p. 2736-2743, Vol. 73, No. 5
0019-9567/05/$08.00+0 doi:10.1128/IAI.73.5.2736-2743.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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