TLR2-mediated microbial sensing by intestinal stem cells coordinates epithelial antimicrobial defense.
Habshush Menachem, A.; Lebon, s.; Killian, C.; Holiar, V.; Sarusi-Portuguez, A.; Davidzohn, N.; Toval, B.; Sochen, C.; Levin-Zaidman, S.; Dezorella, N.; Otikovs, L.; Duran, D.; Kent, I.; Grunewald, M.; Adlung, L.; Biton, M.
Show abstract
Intestinal regeneration and host defense require adaptation to environmental cues, but the mechanisms underlying this coordination remain unclear. We show that intestinal Lgr5 stem cells act as luminal sensors via apically localized Toll-like receptor 2 (TLR2), enabling direct detection of microbiota-derived signals. We identify apical TLR2 activation as a mechanism of luminal sensing in adult stem cells and show that it controls epithelial differentiation, antimicrobial peptide production, and crypt organization, with a particularly strong influence on Paneth cell maturation. Genetic ablation of constitutive, epithelial, or stem cell-specific TLR2 disrupts these processes, leading to impaired antimicrobial defense and altered epithelial composition. Using germ-free mice and human intestinal organoids, we demonstrate that this pathway is microbiota-dependent and evolutionarily conserved, respectively. These findings support a model in which stem cells act as active integrators of environmental information and suggest a broader principle by which barrier tissues couple microbial sensing to regeneration and host protection.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- A longitudinal single-cell therapeutic atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease 98%
- Terminal differentiation and persistence of effector regulatory T cells essential for the prevention of intestinal inflammation 98%
- Restriction of innate Tγδ17 cell plasticity by an AP-1 regulatory axis 98%
Similar papers in this journal
- Isthmus progenitor cells contribute to homeostatic cellular turnover and support regeneration following intestinal injury 98%
- Charting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling 97%
- Patterning and folding of intestinal villi by active mesenchymal dewetting 96%
Similar papers in this journal
- Stratification of enterochromaffin cells by single-cell expression analysis 97%
- Secreted antigen A peptidoglycan hydrolase is essential for Enterococcus faecium cell separation and priming of immune checkpoint inhibitor cancer therapy 96%
- linc-mipep and linc-wrb encode micropeptides that regulate chromatin accessibility in vertebrate-specific neural cells 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.