The ALPK1 pathway drives the inflammatory response to Campylobacter jejuni in human intestinal epithelial cells.

The Gram-negative bacterium Campylobacter jejuni is a major cause of foodborne disease in humans. After infection, C. jejuni rapidly colonizes the mucus layer of the small and large intestine and induces a potent pro-inflammatory response characterized by the production of a large repertoire of cyto...

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Autores principales:	Jiannan Cui, Coco Duizer, Lieneke I Bouwman, Kristel S van Rooijen, Carlos G P Voogdt, Jos P M van Putten, Marcel R de Zoete
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/fa8d0409b68d4f9eaf625093bfa3816b
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spelling	oai:doaj.org-article:fa8d0409b68d4f9eaf625093bfa3816b2021-12-02T20:00:26ZThe ALPK1 pathway drives the inflammatory response to Campylobacter jejuni in human intestinal epithelial cells.1553-73661553-737410.1371/journal.ppat.1009787https://doaj.org/article/fa8d0409b68d4f9eaf625093bfa3816b2021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009787https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The Gram-negative bacterium Campylobacter jejuni is a major cause of foodborne disease in humans. After infection, C. jejuni rapidly colonizes the mucus layer of the small and large intestine and induces a potent pro-inflammatory response characterized by the production of a large repertoire of cytokines, chemokines, and innate effector molecules, resulting in (bloody) diarrhea. The virulence mechanisms by which C. jejuni causes this intestinal response are still largely unknown. Here we show that C. jejuni releases a potent pro-inflammatory compound into its environment, which activates an NF-κB-mediated pro-inflammatory response including the induction of CXCL8, CXCL2, TNFAIP2 and PTGS2. This response was dependent on a functional ALPK1 receptor and independent of Toll-like Receptor and Nod-like Receptor signaling. Chemical characterization, inactivation of the heptose-biosynthesis pathway by the deletion of the hldE gene and in vitro engineering identified the released factor as the LOS-intermediate ADP-heptose and/or related heptose phosphates. During C. jejuni infection of intestinal cells, the ALPK1-NF-κB axis was potently activated by released heptose metabolites without the need for a type III or type IV injection machinery. Our results classify ADP-heptose and/or related heptose phosphates as a major virulence factor of C. jejuni that may play an important role during Campylobacter infection in humans.Jiannan CuiCoco DuizerLieneke I BouwmanKristel S van RooijenCarlos G P VoogdtJos P M van PuttenMarcel R de ZoetePublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 8, p e1009787 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Jiannan Cui Coco Duizer Lieneke I Bouwman Kristel S van Rooijen Carlos G P Voogdt Jos P M van Putten Marcel R de Zoete The ALPK1 pathway drives the inflammatory response to Campylobacter jejuni in human intestinal epithelial cells.
description	The Gram-negative bacterium Campylobacter jejuni is a major cause of foodborne disease in humans. After infection, C. jejuni rapidly colonizes the mucus layer of the small and large intestine and induces a potent pro-inflammatory response characterized by the production of a large repertoire of cytokines, chemokines, and innate effector molecules, resulting in (bloody) diarrhea. The virulence mechanisms by which C. jejuni causes this intestinal response are still largely unknown. Here we show that C. jejuni releases a potent pro-inflammatory compound into its environment, which activates an NF-κB-mediated pro-inflammatory response including the induction of CXCL8, CXCL2, TNFAIP2 and PTGS2. This response was dependent on a functional ALPK1 receptor and independent of Toll-like Receptor and Nod-like Receptor signaling. Chemical characterization, inactivation of the heptose-biosynthesis pathway by the deletion of the hldE gene and in vitro engineering identified the released factor as the LOS-intermediate ADP-heptose and/or related heptose phosphates. During C. jejuni infection of intestinal cells, the ALPK1-NF-κB axis was potently activated by released heptose metabolites without the need for a type III or type IV injection machinery. Our results classify ADP-heptose and/or related heptose phosphates as a major virulence factor of C. jejuni that may play an important role during Campylobacter infection in humans.
format	article
author	Jiannan Cui Coco Duizer Lieneke I Bouwman Kristel S van Rooijen Carlos G P Voogdt Jos P M van Putten Marcel R de Zoete
author_facet	Jiannan Cui Coco Duizer Lieneke I Bouwman Kristel S van Rooijen Carlos G P Voogdt Jos P M van Putten Marcel R de Zoete
author_sort	Jiannan Cui
title	The ALPK1 pathway drives the inflammatory response to Campylobacter jejuni in human intestinal epithelial cells.
title_short	The ALPK1 pathway drives the inflammatory response to Campylobacter jejuni in human intestinal epithelial cells.
title_full	The ALPK1 pathway drives the inflammatory response to Campylobacter jejuni in human intestinal epithelial cells.
title_fullStr	The ALPK1 pathway drives the inflammatory response to Campylobacter jejuni in human intestinal epithelial cells.
title_full_unstemmed	The ALPK1 pathway drives the inflammatory response to Campylobacter jejuni in human intestinal epithelial cells.
title_sort	alpk1 pathway drives the inflammatory response to campylobacter jejuni in human intestinal epithelial cells.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/fa8d0409b68d4f9eaf625093bfa3816b
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The ALPK1 pathway drives the inflammatory response to Campylobacter jejuni in human intestinal epithelial cells.

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