1. Beta-defensin 1 gene polymorphisms at 5' untranslated region are not associated with a susceptibility to recurrent aphthous stomatitis
Anna Kowalska, Zuzanna Ślebioda, Tomasz Woźniak, Robert Zasadziński, Marta Daszkowska, Barbara Dorocka-Bobkowska Arch Oral Biol. 2019 May;101:130-134. doi: 10.1016/j.archoralbio.2019.03.016. Epub 2019 Mar 25.
Objective: The purpose of this study was to evaluate the possible association between two single nucleotide polymorphisms of the β-defensin 1 gene: -20 G > A and -44 C > G at 5 untranslated region and recurrent aphthous stomatitis in a cohort of Polish patients. Design: One hundred and six patients suffering from recurrent aphthous stomatitis and 96 healthy volunteers were genotyped at β-defensin 1-20 G > A and -44 C > G using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. The results were statistically analysed with the difference test between two proportion and chi-square tests with p < 0.05 as a significance level (Dell Statistica data analysis software system, version 13, Dell Inc. 2016). Results: No statistically significant differences between the tested groups were revealed in the genotype distribution for -20 G > A and -44 C > G polymorphisms of the β-defensin 1 gene. Stratification into carriers and non-carriers of alleles did not unequivocally show the single nucleotide polymorphism recognized as a risk factor for recurrent aphthous stomatitis. However, after gender stratification, statistically significant differences in the distribution of some DEFB1 genotypes were observed. Heterozygotes of G[-20]A and C[-44]G genotypes were found more frequently in males with RAS than in males from the control group. Moreover, a significantly higher rate of carriers of the polymorphic *A[-20] allele was found in males with RAS compared to the controls. Conclusions: The role of the tested single nucleotide polymorphisms of the β-defensin 1 gene in the aetiology of recurrent aphthous stomatitis has not been confirmed. Further observations are required to clarify this potential association.
2. β-Defensin: An adroit saviour in teleosts
Sweta Das, Chiranjiv Pradhan, Devika Pillai Fish Shellfish Immunol. 2022 Apr;123:417-430. doi: 10.1016/j.fsi.2022.03.017. Epub 2022 Mar 22.
β-Defensin (BD) is an important first line innate defense molecule with potent antimicrobial and immunomodulatory activities in fish. The signatures of β-defensins are the presence of a net cationic charge and three intramolecular disulfide bonds mediated by six conserved cysteines. It consists of three exons and two introns. The signal peptide is usually conserved and sequence divergence is mostly seen in mature peptide region. The diverse amino acid sequences of matured peptide contribute to a strong positive selection and broad-spectrum antimicrobial activity. It is constitutively expressed in both mucosal as well as systemic sites. Increased expression of β-defensin was mostly reported in bacterial and viral infections in fish. Its role during parasitic and fungal infections is yet to be investigated. β-Defensin isoforms such as BD-1, BD-2, BD-3, BD-4 and BD-5 can be witnessed even in early developmental days to different pathogenic exposure in fish. β-Defensins possess adjuvant properties to enhance antigen-specific immunity promoting both cellular and humoral immune response. It significantly reduces/increases bacterial colonization or viral copy numbers when overexpressed/knockdown. Based on its chemotactic and activating potentials, it can contribute to both innate and adaptive immune responses. With mediated expression, it can also control inflammation. It is potent governing resistance in early developmental days as well. Its expression in pituitary and testis suggests its participation in reproduction and endocrine regulation in fish. Overall, β-defensins is an important member of antimicrobial peptides (AMPs) with multifunctional role in general homeostasis and to pathogen exposure possessing tremendous therapeutic approaches.
3. Intranasal bovine β-defensin-5 enhances antituberculosis immunity in a mouse model by a novel protein-based respiratory mucosal vaccine
Zhengmin Liang, Hao Li, Mengjin Qu, Yiduo Liu, Yuanzhi Wang, Haoran Wang, Yuhui Dong, Yulan Chen, Xin Ge, Xiangmei Zhou Virulence. 2022 Dec;13(1):949-962. doi: 10.1080/21505594.2022.2080342.
Respiratory mucosal immunization is an effective immunization strategy against tuberculosis (TB), and effective mucosal vaccines require adjuvants that can promote protective immunity without deleterious inflammation. Mucosal BCG (Bacille Calmette-Guerin) is effective, but it causes a severe inflammatory response in the lung. A novel less cytotoxic mucosal vaccine AH-PB containing Mycobacterium tuberculosis (Mtb) cell surface antigens Ag85A and HspX (AH), as well as polyinosinic-polycytidylic acid (Poly IC) and bovine neutrophil β-defensin-5 (B5) adjuvants were prepared, with the overarching goal of protecting against TB. Then, the immunogenicity and protective efficacy of these vaccines via the intranasal route were evaluated in a mouse model. Results showed that intranasal AH-PB promoted tissue-resident memory T cells (TRMs) development in the lung, induced antigen-specific antibody response in airway, provided protection against Mycobacterium bovis (M. bovis), conferred better protection than parenteral BCG in the later stage of infection, and boosted the protective immunity generated by BCG in mice. Moreover, both B5 and Poly IC were indispensable for the protection generated by AH-PB. Furthermore, intranasal immunization with AH-B5 fusion vaccines also provided similar protection against M. bovis compared to AH-PB. Collectively, B5-based TB vaccine via the intranasal route is a promising immunization strategy against bovine TB, and this kind of immunization strategy may be applied to human TB vaccine development. These findings highlight the potential importance of B5 as a mucosal adjuvant used in TB vaccines or other respiratory disease vaccines.