Hausmann, Annika ORCID: 0000-0001-8852-3444, Felmy, Boas, Kunz, Leo, Kroon, Sanne, Berthold, Dorothee Lisa, Ganz, Giverny, Sandu, Ioana, Nakamura, Toshihiro ORCID: 0000-0001-5051-4323, Zangger, Nathan Sebastien, Zhang, Yang, Dolowschiak, Tamas, Fattinger, Stefan Alexander, Furter, Markus, Mueller-Hauser, Anna Angelika, Barthel, Manja, Vlantis, Katerina, Wachsmuth, Laurens ORCID: 0000-0003-1701-9384, Kisielow, Jan ORCID: 0000-0002-4482-5202, Tortola, Luigi ORCID: 0000-0002-8480-2080, Heide, Danijela, Heikenwaelder, Mathias, Oxenius, Annette, Kopf, Manfred, Schroeder, Timm, Pasparakis, Manolis ORCID: 0000-0002-9870-0966, Sellin, Mikael Erik and Hardt, Wolf-Dietrich (2021). Intercrypt sentinel macrophages tune antibacterial NF-kappa B responses in gut epithelial cells via TNF. J. Exp. Med., 218 (11). NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-9538

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Abstract

Intestinal epithelial cell (IEC) NF-kappa B signaling regulates the balance between mucosal homeostasis and inflammation. It is not fully understood which signals tune this balance and how bacterial exposure elicits the process. Pure LPS induces epithelial NF-kappa B activation in vivo. However, we found that in mice, IECs do not respond directly to LPS. Instead, tissue-resident lamina propria intercrypt macrophages sense LPS via TLR4 and rapidly secrete TNF to elicit epithelial NF-kappa B signaling in their immediate neighborhood. This response pattern is relevant also during oral enteropathogen infection. The macrophage-TNF-IEC axis avoids responses to luminal microbiota LPS but enables crypt- or tissue-scale epithelial NF-kappa B responses in proportion to the microbial threat. Thereby, intercrypt macrophages fulfill important sentinel functions as first responders to Gram-negative microbes breaching the epithelial barrier. The tunability of this crypt response allows the induction of defense mechanisms at an appropriate scale according to the localization and intensity of microbial triggers.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hausmann, AnnikaUNSPECIFIEDorcid.org/0000-0001-8852-3444UNSPECIFIED
Felmy, BoasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kunz, LeoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kroon, SanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berthold, Dorothee LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ganz, GivernyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sandu, IoanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nakamura, ToshihiroUNSPECIFIEDorcid.org/0000-0001-5051-4323UNSPECIFIED
Zangger, Nathan SebastienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, YangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dolowschiak, TamasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fattinger, Stefan AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Furter, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller-Hauser, Anna AngelikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barthel, ManjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vlantis, KaterinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wachsmuth, LaurensUNSPECIFIEDorcid.org/0000-0003-1701-9384UNSPECIFIED
Kisielow, JanUNSPECIFIEDorcid.org/0000-0002-4482-5202UNSPECIFIED
Tortola, LuigiUNSPECIFIEDorcid.org/0000-0002-8480-2080UNSPECIFIED
Heide, DanijelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heikenwaelder, MathiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oxenius, AnnetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kopf, ManfredUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schroeder, TimmUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pasparakis, ManolisUNSPECIFIEDorcid.org/0000-0002-9870-0966UNSPECIFIED
Sellin, Mikael ErikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hardt, Wolf-DietrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-587640
DOI: 10.1084/jem.20210862
Journal or Publication Title: J. Exp. Med.
Volume: 218
Number: 11
Date: 2021
Publisher: ROCKEFELLER UNIV PRESS
Place of Publication: NEW YORK
ISSN: 1540-9538
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TOLL-LIKE RECEPTOR-4; DENDRITIC CELLS; INTESTINAL MACROPHAGES; SALMONELLA-TYPHIMURIUM; BACTERIAL FLAGELLIN; LIPOPOLYSACCHARIDE; MICE; GENE; EXPRESSION; ALPHAMultiple languages
Immunology; Medicine, Research & ExperimentalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/58764

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