{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T22:00:23Z","timestamp":1784757623505,"version":"3.55.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2013,6,11]],"date-time":"2013-06-11T00:00:00Z","timestamp":1370908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Helicobacter pylori<\/jats:named-content>\n            causes chronic gastritis and avoids elimination by the immune system of the infected host. The commensal bacterium\n            <jats:named-content content-type=\"genus-species\">Lactobacillus acidophilus<\/jats:named-content>\n            has been suggested to exert beneficial effects as a supplement during\n            <jats:named-content content-type=\"genus-species\">H. pylori<\/jats:named-content>\n            eradication therapy. In the present study, we applied whole-genome microarray analysis to compare the immune responses induced in murine bone marrow-derived macrophages (BMDMs) stimulated with\n            <jats:named-content content-type=\"genus-species\">L. acidophilus<\/jats:named-content>\n            ,\n            <jats:named-content content-type=\"genus-species\">H. pylori<\/jats:named-content>\n            , or both bacteria in combination. While\n            <jats:named-content content-type=\"genus-species\">L. acidophilus<\/jats:named-content>\n            induced a Th1-polarizing response characterized by high expression of interferon beta (IFN-\u03b2) and interleukin 12 (IL-12),\n            <jats:named-content content-type=\"genus-species\">H. pylori<\/jats:named-content>\n            strongly induced the innate cytokines IL-1\u03b2 and IL-1\u03b1. In BMDMs prestimulated with\n            <jats:named-content content-type=\"genus-species\">L. acidophilus<\/jats:named-content>\n            ,\n            <jats:named-content content-type=\"genus-species\">H. pylori<\/jats:named-content>\n            blocked the expression of\n            <jats:named-content content-type=\"genus-species\">L. acidophilus<\/jats:named-content>\n            -induced IFN-\u03b2 and IL-12 and suppressed the expression of key regulators of the Rho, Rac, and Cdc42 GTPases. The inhibition of\n            <jats:named-content content-type=\"genus-species\">L. acidophilus<\/jats:named-content>\n            -induced IFN-\u03b2 was independent of\n            <jats:named-content content-type=\"genus-species\">H. pylori<\/jats:named-content>\n            viability and the virulence factor CagPAI; however, a vacuolating cytotoxin (\n            <jats:italic>vacA<\/jats:italic>\n            ) mutant was unable to block IFN-\u03b2. Confocal microscopy demonstrated that the addition of\n            <jats:named-content content-type=\"genus-species\">H. pylori<\/jats:named-content>\n            to\n            <jats:named-content content-type=\"genus-species\">L. acidophilus<\/jats:named-content>\n            -stimulated BMDMs redirects intracellular processing, leading to an accumulation of\n            <jats:named-content content-type=\"genus-species\">L. acidophilus<\/jats:named-content>\n            in the endosomal and lysosomal compartments. Thus, our findings indicate that\n            <jats:named-content content-type=\"genus-species\">H. pylori<\/jats:named-content>\n            inhibits the development of a strong Th1-polarizing response in BMDMs stimulated with\n            <jats:named-content content-type=\"genus-species\">L. acidophilus<\/jats:named-content>\n            by blocking the production of IFN-\u03b2 in a VacA-dependent manner. We suggest that this abrogation is caused by a redirection of the endocytotic pathway in the processing of\n            <jats:named-content content-type=\"genus-species\">L. acidophilus<\/jats:named-content>\n            .\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Approximately half of the world\u2019s population is infected with\n            <jats:named-content content-type=\"genus-species\">Helicobacter pylori<\/jats:named-content>\n            . The factors that allow this pathogen to persist in the stomach and cause chronic infections have not yet been fully elucidated. In particular, how\n            <jats:named-content content-type=\"genus-species\">H. pylori<\/jats:named-content>\n            avoids killing by macrophages, one of the main types of immune cell underlying the epithelium, remains elusive. Here we have shown that the\n            <jats:named-content content-type=\"genus-species\">H. pylori<\/jats:named-content>\n            virulence factor VacA plays a key role by blocking the activation of innate cytokines induced by the probiotic\n            <jats:named-content content-type=\"genus-species\">Lactobacillus acidophilus<\/jats:named-content>\n            in macrophages and suppresses the expression of key regulators required for the organization and dynamics of the intracellular cytoskeleton. Our results identify potential targets for the treatment of\n            <jats:named-content content-type=\"genus-species\">H. pylori<\/jats:named-content>\n            infection and vaccination, since specific inhibition of the toxin VacA possibly allows the activation of an efficient immune response and thereby eradication of\n            <jats:named-content content-type=\"genus-species\">H. pylori<\/jats:named-content>\n            in the host.\n          <\/jats:p>","DOI":"10.1128\/mbio.00609-12","type":"journal-article","created":{"date-parts":[[2013,6,12]],"date-time":"2013-06-12T04:24:20Z","timestamp":1371011060000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":30,"title":["Helicobacter pylori VacA Suppresses Lactobacillus acidophilus-Induced Interferon Beta Signaling in Macrophages via Alterations in the Endocytic 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