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Epithelium-autonomo...
Epithelium-autonomous NAIP/NLRC4 prevents TNF-driven inflammatory destruction of the gut epithelial barrier in Salmonella-infected mice
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- Fattinger, Stefan A. (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab,Swiss Fed Inst Technol, Inst Microbiol, Dept Biol, Zurich, Switzerland
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- Geiser, Petra (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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- Samperio Ventayol, Pilar (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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- Di Martino, Maria Letizia (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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- Furter, Markus (author)
- Swiss Fed Inst Technol, Inst Microbiol, Dept Biol, Zurich, Switzerland.
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- Felmy, Boas (author)
- Swiss Fed Inst Technol, Inst Microbiol, Dept Biol, Zurich, Switzerland.
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- Bakkeren, Erik (author)
- Swiss Fed Inst Technol, Inst Microbiol, Dept Biol, Zurich, Switzerland.
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- Hausmann, Annika (author)
- Swiss Fed Inst Technol, Inst Microbiol, Dept Biol, Zurich, Switzerland.
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- Barthel-Scherrer, Manja (author)
- Swiss Fed Inst Technol, Inst Microbiol, Dept Biol, Zurich, Switzerland.
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- Gül, Ersin (author)
- Swiss Fed Inst Technol, Inst Microbiol, Dept Biol, Zurich, Switzerland.
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- Hardt, Wolf-Dietrich (author)
- Swiss Fed Inst Technol, Inst Microbiol, Dept Biol, Zurich, Switzerland.
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- Sellin, Mikael E. (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi,Swiss Fed Inst Technol, Inst Microbiol, Dept Biol, Zurich, Switzerland
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(creator_code:org_t)
- Springer Nature, 2021
- 2021
- English.
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In: Mucosal Immunology. - : Springer Nature. - 1933-0219 .- 1935-3456. ; 14:3, s. 615-629
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https://uu.diva-port... (primary) (Raw object)
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Abstract
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- The gut epithelium is a critical protective barrier. Its NAIP/NLRC4 inflammasome senses infection by Gram-negative bacteria, including Salmonella Typhimurium (S.Tm) and promotes expulsion of infected enterocytes. During the first ~12–24 h, this reduces mucosal S.Tm loads at the price of moderate enteropathy. It remained unknown how this NAIP/NLRC4-dependent tradeoff would develop during subsequent infection stages. In NAIP/NLRC4-deficient mice, S.Tm elicited severe enteropathy within 72 h, characterized by elevated mucosal TNF (>20 pg/mg) production from bone marrow-derived cells, reduced regeneration, excessive enterocyte loss, and a collapse of the epithelial barrier. TNF-depleting antibodies prevented this destructive pathology. In hosts proficient for epithelial NAIP/NLRC4, a heterogeneous enterocyte death response with both apoptotic and pyroptotic features kept S.Tm loads persistently in check, thereby preventing this dire outcome altogether. Our results demonstrate that immediate and selective removal of infected enterocytes, by locally acting epithelium-autonomous NAIP/NLRC4, is required to avoid a TNF-driven inflammatory hyper-reaction that otherwise destroys the epithelial barrier.
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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- art (subject category)
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- By the author/editor
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Fattinger, Stefa ...
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Geiser, Petra
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Samperio Ventayo ...
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Di Martino, Mari ...
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Furter, Markus
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Felmy, Boas
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Bakkeren, Erik
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Hausmann, Annika
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Barthel-Scherrer ...
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Gül, Ersin
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Hardt, Wolf-Diet ...
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Sellin, Mikael E ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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Mucosal Immunolo ...
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Uppsala University