Beta-defensin 133

Human β-defensin 1 (hBD-1) is a multifaceted antimicrobial peptide being a tumour suppressor and, depending on call of duty, capable of inducing self-nets and neutrophil extracellular traps (NETs) to capture and/or kill bacteria, participates in inflammatory responses in chronic diseases including hBD-3 upregulation and also capable of up/downregulation in the presence of certain species of Lactobacillus sp. Thus, is regulated by host microbiota. Alleles, genotypes and/or altered gene expression of its coding gene, DEFB1, have been associated with several human diseases/conditions ranging from metabolic/chronic (e.g. cancer), infectious (e.g. tuberculosis, HIV/AIDS), inflammatory (gastrointestinal diseases), male infertility and more recently, neurologic (e.g. depression and Alzheimer) and autoimmune diseases (e.g. vitiligo and systemic lupus erythematosus). The present update focuses on novel DEFB1/hBD-1 properties and biomarker features, its biological function and the pharmaceutical potential uses of antimicrobial peptide elicitors (APEs) or the engineered peptide in the treatment of hBD-1-related human diseases.

Background: β-defensins are an excellent antimicrobial peptide against microbial infection in which dendritic cells (DCs) play a crucial role by improving the innate and adaptive immune defense. However, it is unclear whether BDs affect DC maturation. This work aimed to study the effects of mouse β-defensin-14 (MBD-14) on DC maturation. Methods: Via in vitro using mouse bone marrow DCs, the maturation of DCs was evaluated by cell morphological staining, flow cytometry, endocytosis assay, and allogeneic mixed lymphocyte reaction, respectively. And it was also assessed by in vivo establishing a mouse air-pouch model for flow cytometric determination, cytokine analysis, and histological staining. Additionally, CLI-095, an inhibitor of Toll-like receptor-4 (TLR-4), was used to determine whether TLR-4 is possibly involved in DC maturation. Results: It was found MBD-14 promoted DCs to form more filopodia and lamellipodia, increased the expression of DC maturation markers (CD40 and MHC-II), decreased their endocytic capacity, and enhanced T-cell proliferation. The analyses of the air-pouch exudates were consistent with the in vitro results of MBD-14 activating DCs. And when CLI-095 was applied, DC maturation was inhibited partly. Conclusions: This work demonstrates that MBD-14 can promote the maturation of DCs in which TLR-4 is possibly involved.

Human beta-defensins (hBDs) are antimicrobial peptides that have an important role in innate immune responses at epithelial barriers such as the skin. However, the role that hBDs have in initiating cellular immune responses that contribute to antigen-specific adaptive immunity is not well understood. Here we show that one member of the hBD family, hBD3, can induce maturation and T-helper type 1 skewing function in human Langerhans cell-like dendritic cells (LC-DCs). Specifically, hBD3 potently induces phenotypic maturation of LC-DCs, including increased expression of CCR7, which mediates functional chemotactic responses to CCL19 and CCL21. hBD3-stimulated LC-DCs induce strong proliferation of and IFN-γ secretion by naive human T cells. hBD3 also induces phenotypic maturation of primary human skin-migratory DCs derived from human skin explants. These results suggest an important role for hBD3 in inducing DC activation, migration, and polarization. Thus, hBD3 contributes to the integration of innate and adaptive immune responses in the skin, and may be a useful adjuvant for skin immunization and an important factor in the pathophysiology of inflammatory skin diseases.