Paneth cell α-defensins and enteric microbiota in health and disease

Abstract

Antimicrobial peptides are major effectors of innate immunity of multicellular organisms including humans and play a critical role in host defense, and their importance is widely recognized. The epithelium of the intestine is the largest surface area exposed to the outer environment, including pathogens, toxins and foods. The Paneth cell lineage of intestinal epithelial cells produces and secretes α-defensin antimicrobial peptides and functions in innate enteric immunity by removing pathogens and living symbiotically with commensal microbiota to contribute to intestinal homeostasis. Paneth cells secrete α-defensins, HD5 and HD6 in humans and cryptdins in mice, in response to bacterial, cholinergic and other stimuli. The α-defensins have selective activities against bacteria, eliciting potent microbicidal activities against pathogenic bacteria but minimal or no bactericidal activity against commensal bacteria. Therefore, α-defensins regulate the composition of the intestinal microbiota in vivo and play a role in homeostasis of the entire intestine. Recently, relationships between dysbiosis, or abnormal composition of the intestinal microbiota, and diseases such as inflammatory bowel disease and lifestyle diseases including obesity and atherosclerosis have been reported. Because α-defensins regulate the composition of the intestinal microbiota, Paneth cells and their α-defensins may have a key role as one mechanism linking the microbiota and disease.

Expression and Function of Host Defense Peptides at Inflammation Sites

“…The human defensins 5 and 6 (HD5, HD6) are particularly important in preserving the homeostatic equilibrium of the enteric mucosa layer, exhibiting different effects against the essential inducers of their secretion, i.e., various products of the Gram-positive and Gram-negative bacteria [147]. To illustrate, there is a remarkable reduction in the expression levels of HD5 and HD6 by the Paneth cells in inflammatory bowel conditions such as Crohn's disease.…”

Lactobacillus helveticus SBT2171 upregulates the expression of β‐defensin and ameliorates periodontal disease caused by Porphyromonas gingivalis

“…α‐Defensins are expressed in neutrophils and are used to kill phagocytosed bacteria . They are secreted by intestinal Paneth cells and estimated to regulate the intestinal microbiota . β‐Defensins, produced in epithelial cells, show a wide distribution in the body and play critical roles in host defense .…”

“…3 They are secreted by intestinal Paneth cells and estimated to regulate the intestinal microbiota. 4 β-Defensins, produced in epithelial cells, show a wide distribution in the body and play critical roles in host defense. 5 Certain bacterial or inflammatory stimuli upregulate the expression of some β-defensins.…”

Analyzing the Secretome of Gut Microbiota as the Next Strategy For Early Detection of Colorectal Cancer

“…These biomolecules include antibiotics, enzymes, vitamins, amino acids, minerals, energy metabolites, short chain fatty acids (SCFAs), neurotransmitters, hormones, microbial antigens, pathogen‐associated molecular patterns (PAMPs), and toxins, which are “connected” to various organs namely lungs, brain, liver, and muscle via host's circulation . Studies have prevailed on the capability of the host to modulate gut microbial community, for instance, by producing α‐defensins, an antimicrobial peptide responsible to eliminate pathogens and maintain gut homeostasis . The production of immunoglobulin A (IgA) by the hosts helps to maintain gut commensal microbiota, along with the synthesis of microRNA (miRNA) proven to be vital in regulating microbial growth and transcript.…”