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Cathepsin X prevents an effective immune response against Helicobacter pylori infection
Obermajer, Nataša ...
Cathepsin X, a cysteine protease, has been shown to regulate an immune response by activating ?-2 integrin receptors. In this study we demonstrate its role in regulating the immune response to ...infection with H. pylori. The level of cathepsin X was determined in THP-1 monocyte cells primed with H. pylori antigens isolated from subjects suffering from gastritis, who had either eradicated or not the disease after the antibiotic therapy. We show that the specific clinical outcome of H. pylori eradication therapy correlatesstrongly with the membrane expression of cathepsin X in stimulated THP-1 cells, being significantly higher after stimulation with H. pylori strains from those subjects who did not respond to antibiotic therapy. The same antigens elicit a more vigorous immune response, increased expression of MHC II, however trigger inadequate cytokine profile (IFN-? and IL-4) to eradicate the pathogen. We propose that cathepsin X mediated activation of ?-2integrin receptor Mac-1 suppresses the stimulatory signal in the form of cytokines. Cathepsin X co-localizes on the membrane of THP-1 cells with Mac-1 integrin receptor and its inhibition increases homotypic aggregation and mononuclear cell proliferation, events that are associated with low Mac-1 activity. Our study highlights the diversity of the innate immune response to H. pylori antigens leading to either successful eradication of the infection or maintenance of chronic inflammation, revealing cathepsin X location and activity as a regulator of the effectiveness of H. pylori eradication.
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