Peptide YY: a novel Paneth cell antimicrobial peptide that maintains fungal commensalism
Pierre, J. F.; La Torre, D.; Sidebottom, A.; Kambal, A.; Zhu, X.; Tao, Y.; Cham, C. M.; Wang, L.; Harris, K. G.; Zaborina, O.; Alverdy, J. C.; Herzog, H.; Witchley, J.; Noble, S. M.; Leone, V.; Chang, E. B.
Show abstract
Perturbed interactions between the intestinal microbes and host correlate with emergence of fungal virulence. Here we report a previously unknown role for peptide YY (PYY), a described endocrine molecule, as an antimicrobial peptide (AMP) expressed by gut immune epithelial Paneth Cells (PC). PC-PYY differs from other AMPs, including lysozyme, because of limited antibacterial activity, packaging in discrete secretory granules, and selective antifungal activity to virulent hyphae, but not yeast forms of Candida albicans. The latter action is through binding of cationic PC-PYY to the anionic hyphal surface, resulting in membrane disruption and killing. PC-PYY is compartmentalized to surface mucus, which optimizes activity and prevents conversion to endocrine PYY by dipeptidyl peptidase-IV (DPP-IV). We conclude PC-PYY is a unique AMP with selective antifungal activity that maintains gut fungal commensalism. Compromised PC-PYY action from PC dysfunction and/or mucus depletion in ileal Crohns disease may initiate or contribute to disease via fungal pathogenesis. Highlights Paneth Cell PYY (PC-PYY) is an antimicrobial peptide that differs from endocrine-PYY PC-PYY is a selective anti-fungal peptide, targeting the virulent form of C. albicans PC-PYY is separately packaged, retained by mucus, and released by C. albicans hyphae PC-PYY is proposed as essential for maintenance of fungal commensalism in the gut Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY Model for Paneth cell (PC) PYY action and regulation of fungal commensalisms and potential role in the pathogenesis of ileal Crohns Disease (iCD) (A) In a healthy ileum, commensal yeast reside and do not stimulate PYY1-36 release from PCs. (B) Increased virulent hyphae (purple hyphae) results in PYY1-36 release from crypt PCs into the mucus. Hyphae are targeted by PYY1-36 and killed (red hyphae) to manage the increased fungi community in gut. (C) In a diseased ileum such as iCD, hyphal load induces immune activation and increased inflammation through PC dysfunction (gray PCs) and decreased PYY1-36 release or mucus depletion and PC dysfunction. C_FIG_DISPLAY
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Mucolytic bacteria license pathobionts to acquire host-derived nutrients during dietary nutrient restriction 95%
- Lysophosphatidic acid-mediated GPR35 signaling in CX3CR1+ macrophages regulates the intestinal cytokine milieu 94%
- Infection-Induced Elevation of Gut Glycosaminoglycans Fosters Microbiota Expansion in Drosophila melanogaster 94%
Similar papers in this journal
- A history of repeated antibiotic usage leads to microbiota-dependent mucus defects 94%
- An IBD-associated pathobiont synergises with NSAID to promote colitis which is blocked by NLRP3 inflammasome and Caspase-8 inhibitors 94%
- The Autoimmune Susceptibility Gene, PTPN2, Restricts Expansion of a Novel Mouse Adherent-Invasive E. coli 94%
Similar papers in this journal
- Candida albicans commensalism in the oral mucosa is favoured by limited virulence and metabolic adaptation . 94%
- Strain-specific galactose utilization by commensal E. coli mitigates Salmonella establishment in the gut 94%
- Defined roles for the Staphylococcus aureus POT transporter DtpT in di/tripeptide uptake and glutathione utilisation inside human macrophages 94%
"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.