Cathepsin X prevents an effective immune response against Helicobacter pylori infection.
Cathepsin X, a cysteine protease, has been shown to regulate an immune response by activating beta-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 correlates strongly 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-gamma and IL-4) to eradicate the pathogen. We propose that cathepsin X mediated activation of beta-2 integrin 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.
Obermajer
Natasa
N
University of Ljubljana, Faculty of Pharmacy, Department of Pharmaceutical Biology, Askerceva 7, 1000 Ljubljana, Slovenia. natasa.obermajer@ffa.uni-lj.si
Magister
Spela
S
Kopitar
Andreja Natasa
AN
Tepes
Bojan
B
Ihan
Alojz
A
Kos
Janko
J
D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D056657:Cathepsin K; D002403:Cathepsins / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D024881:Drug Resistance, Bacterial; D005802:Genes, MHC Class II; D016481:Helicobacter Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D016480:Helicobacter pylori / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000378:metabolism
D000900:Anti-Bacterial Agents; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D015847:Interleukin-4; D007371:Interferon-gamma; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K