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Intercrypt sentinel macrophages tune antibacterial NF-kappa B responses in gut epithelial cells via TNF

Hausmann, Annika (author)
Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland.
Felmy, Boas (author)
Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland.
Kunz, Leo (author)
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland.
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Kroon, Sanne (author)
Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland.
Berthold, Dorothee Lisa (author)
Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland.
Ganz, Giverny (author)
Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland.
Sandu, Ioana (author)
Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland.
Nakamura, Toshihiro (author)
Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland.
Zangger, Nathan Sebastien (author)
Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland.
Zhang, Yang (author)
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland.
Dolowschiak, Tamas (author)
Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland.
Fattinger, Stefan A. (author)
Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland.
Furter, Markus (author)
Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland.
Müller-Hauser, Anna Angelika (author)
Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland.
Barthel, Manja (author)
Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland.
Vlantis, Katerina (author)
Univ Cologne, Inst Genet, Cologne Excellence Cluster Cellular Stress Respon, Cologne, Germany.
Wachsmuth, Laurens (author)
Univ Cologne, Inst Genet, Cologne Excellence Cluster Cellular Stress Respon, Cologne, Germany.
Kisielow, Jan (author)
Swiss Fed Inst Technol, Dept Biol, Inst Mol Hlth Sci, Zurich, Switzerland.
Tortola, Luigi (author)
Swiss Fed Inst Technol, Dept Biol, Inst Mol Hlth Sci, Zurich, Switzerland.
Heide, Danijela (author)
German Canc Res Ctr, Div Chron Inflammat & Canc, Heidelberg, Germany.
Heikenwälder, Mathias (author)
German Canc Res Ctr, Div Chron Inflammat & Canc, Heidelberg, Germany.
Oxenius, Annette (author)
Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland.
Kopf, Manfred (author)
Swiss Fed Inst Technol, Dept Biol, Inst Mol Hlth Sci, Zurich, Switzerland.
Schroeder, Timm (author)
Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland.
Pasparakis, Manolis (author)
Univ Cologne, Inst Genet, Cologne Excellence Cluster Cellular Stress Respon, Cologne, Germany.
Sellin, Mikael E. (author)
Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi,Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland.
Hardt, Wolf-Dietrich (author)
Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland.
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Swiss Fed Inst Technol, Dept Biol, Inst Microbiol, Zurich, Switzerland Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland. (creator_code:org_t)
2021-09-16
2021
English.
In: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 218:11
Related links:
https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

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