The Antimicrobial Peptide CRAMP Is Essential for Colon Homeostasis by Maintaining Microbiota Balance

Yoshimura, Teizo; McLean, Mairi H; Dzutsev, Amiran; Yao, Xiaohong; Chen, Keqiang; Huang, Jiaqiang; Gong, Wanghua; Zhou, Jiamin; Xiang, Yi; Badger, Jonathan H.; Ó'hUigín, Colm; Thovarai, Vishal; Tessarollo, Lino; Durum, Scott K.; Trinchieri, Giorgio; Bian, Xiu Wu; Wang, Ji Ming

doi:10.4049/jimmunol.1602073

Cited by 58 publications

(68 citation statements)

References 26 publications

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“…As the microbiome is associated with the development of these disorders, it will be interesting to examine whether differences in microbiome composition in chemerin and CMKLR1 KO mice under stressed conditions such as a HFD or chemically-induced colitis influence the development of inflammatory and metabolic diseases. Additionally, in the current study we co-housed wildtype and KO mice at weaning, and it is possible that transfer of microbes occurred between genotypes in the same cage as previously demonstrated ( Yoshimura et al, 2018 ). Therefore, future studies that compare the microbiota composition of mice housed alone versus with a different genotype may identify further differences in microbiome profiles.…”

Section: Discussionmentioning

confidence: 94%

The impact of chemerin or chemokine-like receptor 1 loss on the mouse gut microbiome

Dranse

Zheng

Comeau

et al. 2018

PeerJ

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Chemerin is an adipocyte derived signalling molecule (adipokine) that serves as a ligand activator of Chemokine-like receptor 1(CMKLR1). Chemerin/CMKLR1 signalling is well established to regulate fundamental processes in metabolism and inflammation. The composition and function of gut microbiota has also been shown to impact the development of metabolic and inflammatory diseases such as obesity, diabetes and inflammatory bowel disease. In this study, we assessed the microbiome composition of fecal samples isolated from wildtype, chemerin, or CMKLR1 knockout mice using Illumina-based sequencing. Moreover, the knockout mice and respective wildtype mice used in this study were housed at different universities allowing us to compare facility-dependent effects on microbiome composition. While there was no difference in alpha diversity within samples when compared by either facility or genotype, we observed a dramatic difference in the presence and abundance of numerous taxa between facilities. There were minor differences in bacterial abundance between wildtype and chemerin knockout mice, but significantly more differences in taxa abundance between wildtype and CMKLR1 knockout mice. Specifically, CMKLR1 knockout mice exhibited decreased abundance of Akkermansia and Prevotella, which correlated with body weight in CMKLR1 knockout, but not wildtype mice. This is the first study to investigate a linkage between chemerin/CMKLR1 signaling and microbiome composition. The results of our study suggest that chemerin/CMKLR1 signaling influences metabolic processes through effects on the gut microbiome. Furthermore, the dramatic difference in microbiome composition between facilities might contribute to discrepancies in the metabolic phenotype of CMKLR1 knockout mice reported by independent groups. Considered altogether, these findings establish a foundation for future studies to investigate the relationship between chemerin signaling and the gut microbiome on the development and progression of metabolic and inflammatory disease.

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Section: Discussionmentioning

confidence: 94%

The impact of chemerin or chemokine-like receptor 1 loss on the mouse gut microbiome

Dranse

Zheng

Comeau

et al. 2018

PeerJ

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“…In addition, the interaction of CHDP and the microbiome in mucosal immunity is a rapidly emerging area of research. Although beyond the scope of this review, this exciting area of research suggests the potential for CHDP-mediated selectivity in control of the microbiome [130][131][132][133] , but also the potential for components of the microbiome to contribute to the regulation of CHDP expression. Further research on CHDP-microbiome interaction may enhance understanding of the consequences of microbial dysbiosis in disease states, aging and following treatment with broad-spectrum antibiotics.…”

Section: [H2] Immune Activationmentioning

confidence: 99%

Antimicrobial host defence peptides: functions and clinical potential

Mookherjee

Anderson

Haagsman

et al. 2020

Nat Rev Drug Discov

838

955

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Cationic host defence peptides (CHDP), also known as antimicrobial peptides, are naturally-occurring peptides which can combat infections through their direct microbicidal properties and/or by influencing the host's immune responses. The unique ability of CHDP to control infections as well as resolve harmful inflammation has generated interest in harnessing the properties of these peptides to develop new therapies for infectious diseases, chronic inflammatory disorders and wound healing. Various strategies have been employed to design synthetic optimized peptides, with negligible toxicity. Here, we focus on the progress made in understanding the scope of functions of CHDP and the emerging potential clinical applications of CHDP-based therapies. This has led to the adoption of the current name for this family of peptides, Cationic Host Defence Peptides, which encompasses the wide range of described functions. Over the last three decades there has been substantial interest in therapeutically harnessing CHDP, with more than 5000 papers published in this area of research since 2017 alone. These include the examination of potential clinical uses for CHDP ranging from infections including multidrug-resistant bacteria 16-19 , to chronic inflammatory diseases such as arthritis 20 , asthma 21 and colitis 22 , as well as some cancers 23. Peptide-based therapeutics currently in clinical trials are primarily for the treatment of infections such as respiratory, oral and catheter-related infections, and for wound healing (see http://dramp.cpu-bioinfor.org/browse/ClinicalTrialsData.php). This review will provide an overview of current understanding of the scope of functions of CHDP, primarily from eukaryotes. Emerging therapeutic applications of these peptides, current clinical trials and the associated clinical developmental challenges will be discussed. Although there is increasing interest in the development of non-peptide mimics of CHDP for therapeutic application, such as peptoid analogs (reviewed in 24), a comprehensive discussion of these approaches is beyond the scope of this review. [H1] Naturally occurring CHDP The antimicrobial peptide database has catalogued more than 2600 natural antimicrobial peptides, including those annotated as immunomodulatory 25. The major families of CHDP from eukaryotes that are of interest from a drug discovery perspective are summarized below. [H2] Vertebrate CHDP CHDP from vertebrates have an essential role in the first line of defense against microbial pathogens. Upon infection, CHDP can kill pathogens through diverse mechanisms 26-31 (discussed below), acting rapidly and directly on the pathogen when present in high local concentrations, or indirectly to modify components of host defense. These peptides exhibit immunomodulatory activities that can be either pro-or anti-inflammatory depending on the phase of the infection (see below) 12-14,29. CHDP from vertebrates are amphipathic peptides containing amino acids with hydrophilic and hydrophobic side chains at opposite sides of the molec...

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“…Six DEGs are shared in all groups, including four immune-related genes, including Cebpd, Camp, Cd177, and Fcnb. Camp was reported to be critical in maintaining colon microbiota balance and supports mucosal homeostasis, anti-inflammatory responses, and protection from carcinogenesis [26]. While mouse ficolin-B (Fcnb) was a functional member of the ficolin family activating complement via the lectin pathway [27].…”

Section: Analysis Of Degsmentioning

confidence: 99%

Early IgG Response to Foot and Mouth Disease Vaccine Formulated with a Vegetable Oil Adjuvant

et al. 2019

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The present study evaluated soybean oil (SO) containing vitamin E (VE) and ginseng saponins (GS) (SO-VE-GS) for their adjuvant effect on foot-and-mouth disease (FMD) vaccine. Since mineral oil ISA 206 is a common adjuvant used in the FMD vaccine, it was used as a control adjuvant in this study. VE and GS were found to have a synergistic adjuvant effect. When mice were immunized with the FMD vaccine emulsified in SO with VE and GS, significantly higher serum IgG, IgG1, and IgG2a were found than VE and GS used alone. SO-VE-GS and ISA 206 behaved differently in adjuvant activities. When mice were immunized with the FMD vaccine adjuvanted with SO-VE-GS, significantly higher and earlier production of serum IgG was found than that adjuvanted with ISA 206. Although both adjuvants significantly increased the number of bone marrow plasma cells, a stimulation index of lymphocytes (SI) as well as the production of IL-4 and IL-6, SO-VE-GS promoted significantly higher SI and the ratio of CD4+/CD8+ T cells with production of increased IFN-γ and decreased TGF-β1 as compared with the ISA 206 group. The data suggested that SO-VE-GS activated Th1/Th2 immune responses. Transcriptome analysis of splenocytes showed that differentially expressed genes (DEGs), immune-related gene ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched in the SO-VE-GS group. Therefore, the potent adjuvant effect of SO-VE-GS on the FMD vaccine may be attributed to the immune-related gene profile expressed in lymphocytes. Due to its plant origin and due to being much cheaper than imported mineral oil ISA 206, SO-VE-GS deserves further study in relation to vaccines used in food animals.

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The Antimicrobial Peptide CRAMP Is Essential for Colon Homeostasis by Maintaining Microbiota Balance

Cited by 58 publications

References 26 publications

The impact of chemerin or chemokine-like receptor 1 loss on the mouse gut microbiome

The impact of chemerin or chemokine-like receptor 1 loss on the mouse gut microbiome

Antimicrobial host defence peptides: functions and clinical potential

Early IgG Response to Foot and Mouth Disease Vaccine Formulated with a Vegetable Oil Adjuvant

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