Human Beta-defensins: Differential Activity against Candidal Species and Regulation by <i>Candida albicans</i>

Feng, Zhihui; Jiang, Bin; Chandra, Jyotsna; Ghannoum, Mahmoud A.; Nelson, Suchitra; Weinberg, Aaron

doi:10.1177/154405910508400509

Cited by 153 publications

(138 citation statements)

References 28 publications

(24 reference statements)

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“…5). Finally, in line with previous in vitro findings (15)(16)(17), DEFB1 expression was inversely correlated with the carriage of C. albicans (18) and the humoral response to mannan, a major epitope for anti-Saccharomyces cerevisiae antibody (ASCA) production (17). C. albicans colonization was significantly increased in CD patients and was identified as an immunogen for ASCA (19), a serologic marker associated mainly with colonic involvement in CD (23).…”

Section: Discussionsupporting

confidence: 87%

Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon

Peyrin–Biroulet

Beisner

Wang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

178

137

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Crohn's disease (CD), a major form of human inflammatory bowel disease, is characterized by primary immunodeficiencies. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is essential for intestinal homeostasis in response to both dietaryand microbiota-derived signals. Its role in host defense remains unknown, however. We show that PPARγ functions as an antimicrobial factor by maintaining constitutive epithelial expression of a subset of β-defensin in the colon, which includes mDefB10 in mice and DEFB1 in humans. Colonic mucosa of Pparγ mutant animals shows defective killing of several major components of the intestinal microbiota, including Candida albicans, Bacteroides fragilis, Enterococcus faecalis, and Escherichia coli. Neutralization of the colicidal activity using an anti-mDefB10 blocking antibody was effective in a PPARγ-dependent manner. A functional promoter variant that is required for DEFB1 expression confers strong protection against Crohn's colitis and ileocolitis (odds ratio, 0.559; P = 0.018). Consistently, colonic involvement in CD is specifically linked to reduced expression of DEFB1 independent of inflammation. These findings support the development of PPARγ-targeting therapeutic and/or nutritional approaches to prevent colonic inflammation by restoring antimicrobial immunity in CD.β-defensin 1 | Crohn's disease | microbiota | nutrition | PPAR-γ

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Section: Discussionsupporting

confidence: 87%

Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon

Peyrin–Biroulet

Beisner

Wang

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

178

137

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“…Specifically, the FTOM and EpiOral™ models constitutively expressed hBD 1 & 3 in a manner similar to normal oral mucosa [29], whereas the RHOE model lacked expression of these proteins. Furthermore, when infected with C. albicans, hBD2 was markedly up-regulated in the FTOM and EpiOral™ models in a similar manner to that described for the normal oral mucosa [28,29], whereas the RHOE model showed only very minor increases in expression. The disparities in the expression of these immune molecules between models are likely to be due to genetic differences between normal and tumor cells where gene expression of cytokines, pattern recognition receptors, anti-microbial peptides and cell signaling molecules are often dysregulated [37,38].…”

Section: Discussionsupporting

confidence: 66%

“…Expression of hBD2, which has been previously shown to be up-regulated in Candida-infected oral epithelium [28,29], was examined in the mucosal models. All three models displayed little or no staining for hBD2 in uninfected controls (Fig.…”

Section: Differential Expression Of Human β-Defensin 2 (Hbd2) By Mucomentioning

confidence: 99%

Evaluation of tissue engineered models of the oral mucosa to investigate oral candidiasis

Yadev

Murdoch

Saville

et al. 2011

Microbial Pathogenesis

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Candida albicans is a commensal organism that can be isolated from the majority of healthy individuals. However, in certain susceptible individuals C.albicans can become pathogenic leading to the mucocutaneous infection; oral candidiasis. Murine models and in vitro monolayer cultures have generated some data on the likely virulence and host factors that contribute to oral candidiasis but these models have limitations. Recently, tissue engineered oral mucosal models have been developed to mimic the normal oral mucosa but little information is available on their true representation. In this study we assessed the histological features of three different tissue engineered oral mucosal models compared to the normal oral mucosa and analysed both cell damage and cytokine release following infection with C.albicans. Models comprised of normal oral keratinocytes and a fibroblast-containing matrix displayed more similar immunohistological and proliferation characteristics to normal mucosa compared to models composed of an oral carcinoma cell line. Although all models were invaded and damaged by C.albicabs in a similar manner, the cytokine response was much more pronounced in models containing normal keratinocytes. These data suggest that models based on normal keratinocytes atop a fibroblast-containing connective tissue will significantly aid in dissecting the molecular pathogenesis of oral candidiasis.

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“…These antimicrobial peptides display their bactericidal activity against Gram-positive and -negative bacteria [11,12,[35][36][37]. HBD-1 and hBD-3 share the ability to inactivate Candida species [38,39]. HBD-3 was shown to inhibit infection of HSV, whereas hBD-1 and -2 show no anti-viral effects [29].…”

Section: Antimicrobial Activitymentioning

confidence: 99%

Human Defensins: Potential Tools for Clinical Applications

Winter

Wenghoefer

2012

Polymers

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As components of the innate immune system, antimicrobial peptides in the form of human defensins play an important role in host defense by serving as the epithelial layer’s biochemical barrier against local infections. Recent studies have shown these molecules to have far more additional cellular functions besides their antimicrobial activity. Defensins play a role in cell division, attraction and maturation of immune cells, differentiation and reorganization of epithelial tissues, wound healing and tumor suppression. This multitude of function makes human defensins appear to be excellent tools for therapeutic approaches. These antimicrobial peptides may be used directly as a remedy against bacterial and viral infections. Furthermore, the application of human defensins can be used to promote wound healing and epithelial reorganization. In particular, human β-defensins have a strong impact on osteoblast proliferation and differentiation. Human β-defensins have already been applied as a vaccination against HIV-1. Another potentially useful characteristic of defensins is their suitability as diagnostic markers in cancer therapy. In particular, α-defensins have already been used for this purpose. Human α-defensin-3, for example, has been described as a tumor marker for lymphocytes. High gene expression levels of α-defensin-3 and -4 have been detected in benign oral neoplasia, α-defensin-6 is considered to be a tumor marker for colon cancer.

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Human Beta-defensins: Differential Activity against Candidal Species and Regulation by Candida albicans

Cited by 153 publications

References 28 publications

Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon

Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon

Evaluation of tissue engineered models of the oral mucosa to investigate oral candidiasis

Human Defensins: Potential Tools for Clinical Applications

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