<named-content content-type="genus-species">Helicobacter pylori</named-content> VacA Suppresses <named-content content-type="genus-species">Lactobacillus acidophilus</named-content>-Induced Interferon Beta Signaling in Macrophages via Alterations in the Endocytic Pathway

ABSTRACT Helicobacter pylori causes chronic gastritis and avoids elimination by the immune system of the infected host. The commensal bacterium Lactobacillus acidophilus has been suggested to exert beneficial effects as a supplement during H. pylori eradication therapy. In the present study, we appl...

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Autores principales:	Gudrun Weiss, Sam Forster, Aaron Irving, Michelle Tate, Richard L. Ferrero, Paul Hertzog, Hanne Frøkiær, Maria Kaparakis-Liaskos
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0a98a2d44f0b4a3fb549ebff0442f56b
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spelling	oai:doaj.org-article:0a98a2d44f0b4a3fb549ebff0442f56b2021-11-15T15:40:05Z<named-content content-type="genus-species">Helicobacter pylori</named-content> VacA Suppresses <named-content content-type="genus-species">Lactobacillus acidophilus</named-content>-Induced Interferon Beta Signaling in Macrophages via Alterations in the Endocytic Pathway10.1128/mBio.00609-122150-7511https://doaj.org/article/0a98a2d44f0b4a3fb549ebff0442f56b2013-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00609-12https://doaj.org/toc/2150-7511ABSTRACT Helicobacter pylori causes chronic gastritis and avoids elimination by the immune system of the infected host. The commensal bacterium Lactobacillus acidophilus has been suggested to exert beneficial effects as a supplement during H. pylori 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 L. acidophilus, H. pylori, or both bacteria in combination. While L. acidophilus induced a Th1-polarizing response characterized by high expression of interferon beta (IFN-β) and interleukin 12 (IL-12), H. pylori strongly induced the innate cytokines IL-1β and IL-1α. In BMDMs prestimulated with L. acidophilus, H. pylori blocked the expression of L. acidophilus-induced IFN-β and IL-12 and suppressed the expression of key regulators of the Rho, Rac, and Cdc42 GTPases. The inhibition of L. acidophilus-induced IFN-β was independent of H. pylori viability and the virulence factor CagPAI; however, a vacuolating cytotoxin (vacA) mutant was unable to block IFN-β. Confocal microscopy demonstrated that the addition of H. pylori to L. acidophilus-stimulated BMDMs redirects intracellular processing, leading to an accumulation of L. acidophilus in the endosomal and lysosomal compartments. Thus, our findings indicate that H. pylori inhibits the development of a strong Th1-polarizing response in BMDMs stimulated with L. acidophilus by blocking the production of IFN-β in a VacA-dependent manner. We suggest that this abrogation is caused by a redirection of the endocytotic pathway in the processing of L. acidophilus. IMPORTANCE Approximately half of the world’s population is infected with Helicobacter pylori. The factors that allow this pathogen to persist in the stomach and cause chronic infections have not yet been fully elucidated. In particular, how H. pylori avoids killing by macrophages, one of the main types of immune cell underlying the epithelium, remains elusive. Here we have shown that the H. pylori virulence factor VacA plays a key role by blocking the activation of innate cytokines induced by the probiotic Lactobacillus acidophilus 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 H. pylori infection and vaccination, since specific inhibition of the toxin VacA possibly allows the activation of an efficient immune response and thereby eradication of H. pylori in the host.Gudrun WeissSam ForsterAaron IrvingMichelle TateRichard L. FerreroPaul HertzogHanne FrøkiærMaria Kaparakis-LiaskosAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 3 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Gudrun Weiss Sam Forster Aaron Irving Michelle Tate Richard L. Ferrero Paul Hertzog Hanne Frøkiær Maria Kaparakis-Liaskos <named-content content-type="genus-species">Helicobacter pylori</named-content> VacA Suppresses <named-content content-type="genus-species">Lactobacillus acidophilus</named-content>-Induced Interferon Beta Signaling in Macrophages via Alterations in the Endocytic Pathway
description	ABSTRACT Helicobacter pylori causes chronic gastritis and avoids elimination by the immune system of the infected host. The commensal bacterium Lactobacillus acidophilus has been suggested to exert beneficial effects as a supplement during H. pylori 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 L. acidophilus, H. pylori, or both bacteria in combination. While L. acidophilus induced a Th1-polarizing response characterized by high expression of interferon beta (IFN-β) and interleukin 12 (IL-12), H. pylori strongly induced the innate cytokines IL-1β and IL-1α. In BMDMs prestimulated with L. acidophilus, H. pylori blocked the expression of L. acidophilus-induced IFN-β and IL-12 and suppressed the expression of key regulators of the Rho, Rac, and Cdc42 GTPases. The inhibition of L. acidophilus-induced IFN-β was independent of H. pylori viability and the virulence factor CagPAI; however, a vacuolating cytotoxin (vacA) mutant was unable to block IFN-β. Confocal microscopy demonstrated that the addition of H. pylori to L. acidophilus-stimulated BMDMs redirects intracellular processing, leading to an accumulation of L. acidophilus in the endosomal and lysosomal compartments. Thus, our findings indicate that H. pylori inhibits the development of a strong Th1-polarizing response in BMDMs stimulated with L. acidophilus by blocking the production of IFN-β in a VacA-dependent manner. We suggest that this abrogation is caused by a redirection of the endocytotic pathway in the processing of L. acidophilus. IMPORTANCE Approximately half of the world’s population is infected with Helicobacter pylori. The factors that allow this pathogen to persist in the stomach and cause chronic infections have not yet been fully elucidated. In particular, how H. pylori avoids killing by macrophages, one of the main types of immune cell underlying the epithelium, remains elusive. Here we have shown that the H. pylori virulence factor VacA plays a key role by blocking the activation of innate cytokines induced by the probiotic Lactobacillus acidophilus 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 H. pylori infection and vaccination, since specific inhibition of the toxin VacA possibly allows the activation of an efficient immune response and thereby eradication of H. pylori in the host.
format	article
author	Gudrun Weiss Sam Forster Aaron Irving Michelle Tate Richard L. Ferrero Paul Hertzog Hanne Frøkiær Maria Kaparakis-Liaskos
author_facet	Gudrun Weiss Sam Forster Aaron Irving Michelle Tate Richard L. Ferrero Paul Hertzog Hanne Frøkiær Maria Kaparakis-Liaskos
author_sort	Gudrun Weiss
title	<named-content content-type="genus-species">Helicobacter pylori</named-content> VacA Suppresses <named-content content-type="genus-species">Lactobacillus acidophilus</named-content>-Induced Interferon Beta Signaling in Macrophages via Alterations in the Endocytic Pathway
title_short	<named-content content-type="genus-species">Helicobacter pylori</named-content> VacA Suppresses <named-content content-type="genus-species">Lactobacillus acidophilus</named-content>-Induced Interferon Beta Signaling in Macrophages via Alterations in the Endocytic Pathway
title_full	<named-content content-type="genus-species">Helicobacter pylori</named-content> VacA Suppresses <named-content content-type="genus-species">Lactobacillus acidophilus</named-content>-Induced Interferon Beta Signaling in Macrophages via Alterations in the Endocytic Pathway
title_fullStr	<named-content content-type="genus-species">Helicobacter pylori</named-content> VacA Suppresses <named-content content-type="genus-species">Lactobacillus acidophilus</named-content>-Induced Interferon Beta Signaling in Macrophages via Alterations in the Endocytic Pathway
title_full_unstemmed	<named-content content-type="genus-species">Helicobacter pylori</named-content> VacA Suppresses <named-content content-type="genus-species">Lactobacillus acidophilus</named-content>-Induced Interferon Beta Signaling in Macrophages via Alterations in the Endocytic Pathway
title_sort	<named-content content-type="genus-species">helicobacter pylori</named-content> vaca suppresses <named-content content-type="genus-species">lactobacillus acidophilus</named-content>-induced interferon beta signaling in macrophages via alterations in the endocytic pathway
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/0a98a2d44f0b4a3fb549ebff0442f56b
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<named-content content-type="genus-species">Helicobacter pylori</named-content> VacA Suppresses <named-content content-type="genus-species">Lactobacillus acidophilus</named-content>-Induced Interferon Beta Signaling in Macrophages via Alterations in the Endocytic Pathway

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