Article

Intestinal antimicrobial peptides during homeostasis, infection, and disease

Department of Medicine, Immunology Institute, Mount Sinai School of Medicine New York, NY, USA.
Frontiers in Immunology 10/2012; 3:310. DOI: 10.3389/fimmu.2012.00310
Source: PubMed

ABSTRACT Antimicrobial peptides (AMPs), including defensins and cathelicidins, constitute an arsenal of innate regulators of paramount importance in the gut. The intestinal epithelium is exposed to myriad of enteric pathogens and these endogenous peptides are essential to fend off microbes and protect against infections. It is becoming increasingly evident that AMPs shape the composition of the commensal microbiota and help maintain intestinal homeostasis. They contribute to innate immunity, hence playing important functions in health and disease. AMP expression is tightly controlled by the engagement of pattern recognition receptors (PRRs) and their impairment is linked to abnormal host responses to infection and inflammatory bowel diseases (IBD). In this review, we provide an overview of the mucosal immune barriers and the intricate crosstalk between the host and the microbiota during homeostasis. We focus on the AMPs and pay particular attention to how PRRs promote their secretion in the intestine. Furthermore, we discuss their production and main functions in three different scenarios, at steady state, throughout infection with enteric pathogens and IBD.

Download full-text

Full-text

Available from: Garabet Yeretssian, May 25, 2014
0 Followers
 · 
85 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Deoxynivalenol (DON) affects animal and human health and targets the gastrointestinal tract. The objective of this study was to evaluate the ability of composite antimicrobial peptides (CAP) to repair intestinal injury in piglets challenged with DON. A total of 28 piglets (Duroc x Landrace x Large Yorkshire) weaned at 28 d of age were randomly assigned to receive 1 of 4 treatments (7 pigs/treatment): negative control, basal diet (NC), basal diet + 0.4% composite antimicrobial peptide (CAP), basal diet + 4 ppm DON (DON), and basal diet + 4 ppm DON + 0.4% CAP (DON + CAP). After an adaptation period of 7 d, blood samples were collected on d 15 and 30 after the initiation of treatment for determinations of the concentrations of D-lactate and diamine oxidase. At the end of the study, all piglets were slaughtered to obtain small intestines for the determination of intestinal morphology, epithelial cell proliferation, and protein expression in the mammalian target of rapamycin (mTOR) signaling pathway. The results showed that DON increased serum levels of D-lactate and diamine oxidase, and these values in the CAP and DON + CAP treatments were lower than those in the NC and DON treatments, respectively (P < 0.05). The villous height/crypt depth in the jejunum and ileum and the goblet cell number in the ileum in the CAP and DON + CAP treatments were greater than those in the NC and DON treatments (P < 0.05). The proliferating cell nuclear antigen (PCNA) labeling indexes for the jejunum and ileum in the DON + CAP treatment were greater than those in the DON treatment (P < 0.05). The DON decreased (P < 0.05) the relative protein expression levels of phosphorylated Akt (Protein Kinase B) and mTOR in the jejunal and ileal mucosa and of phosphorylated 4E-binding protein 1 (p-4EBP1) in the jejunal mucosa, while CAP increased (P < 0.05) the protein expression levels of p-4EBP1 in the jejunum. These findings showed that DON could enhance intestinal permeability, damage villi, cause epithelial cell apoptosis and inhibit protein synthesis, whereas CAP improved intestinal morphology and promoted intestinal epithelial cell proliferation and protein synthesis, indicating that CAP may repair the intestinal injury induced by DON.
    Journal of Animal Science 08/2013; 91(10). DOI:10.2527/jas.2013-6427 · 1.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Under continual attack from both microbial pathogens and multicellular parasites, insects must cope with immune challenges every day of their lives. However, this has not prevented them from becoming the most successful group of animals on the planet. Insects possess highly-developed innate immune systems which have been fine-tuned by an arms race with pathogens spanning hundreds of millions of years of evolutionary history. Recent discoveries are revealing both an unexpected degree of specificity and an indication of immunological memory - the functional hallmark of vertebrate immunity. The study of insect immune systems has accelerated rapidly in recent years and is now becoming an important interdisciplinary field. Furthermore, insects are a phenomenally rich and diverse source of antimicrobial chemicals. Some of these are already being seriously considered as potential therapeutic agents to control microbes such as MRSA. Despite a burgeoning interest in the field, this is the first book to provide a coherent synthesis and is clearly structured around two broadly themed sections: mechanisms of immunity and evolutionary ecology. This novel text adopts an interdisciplinary and concept-driven approach, integrating insights from immunology, molecular biology, ecology, evolutionary biology, parasitology, and epidemiology. It features contributions from an international team of leading experts. Insect Infection and Immunity is suitable for both graduate students and researchers interested in insect immunity from either an evolutionary, genetical, physiological or molecular perspective. Due to its interdisciplinary and concept-driven approach, it will also appeal to a broader audience of immunologists, parasitologists and evolutionary biologists requiring a concise overview.
    1 01/2009: pages 13-33; OUP Oxford.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Antimicrobial peptides may influence the pathogenesis and course of inflammatory bowel disease (IBD). We sought to clarify the role of the antimicrobial glycoprotein lipocalin 2 (LCN2) in the colon by determining its localization and regulation in IBD. Following a microarray gene expression study of colonic biopsies from a large IBD population (n=133), LCN2 was localized using immunohistochemistry and in situ hybridization. Moreover, we examined the regulation of LCN2 in HT-29 cells with a panel of Pattern Recognition Receptors (PRRs) and sought evidence by immunohistochemistry that the most relevant PRR, the Toll-like receptor TLR3, was indeed expressed in colonic epithelium in IBD.LCN2 was among the ten most upregulated genes in both active ulcerative colitis (UCa) and active Crohn`s disease (CDa) vs healthy controls. LCN2 protein was found in both epithelial cells and infiltrating neutrophils, while mRNA synthesis was located solely to epithelial cells indicating that de novo synthesis and thus regulation of LCN2 as measured in the gene expression analysis takes place in the mucosal epithelial cells. LCN2 is a putative biomarker in feces for intestinal inflammation, different from calprotectin due to its epithelial site of synthesis. LCN2 release from the colonic epithelial cell line HT-29 was enhanced by both IL-1β and the TLR3 ligand poly(I:C), and TLR3 was shown to be constitutively expressed in colonic epithelial cells and markedly increased during inflammation.
    Clinical & Experimental Immunology 05/2013; 173(3). DOI:10.1111/cei.12136 · 3.28 Impact Factor