{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Human β‐defensin 1 (hBD‐1), encoded by the DEFB1 gene, is a critical component of the innate immune barrier at epithelial surfaces. Constitutively expressed in tissues such as the lung, colon, and oral cavity, hBD‐1 contributes to host defense by directly killing a range of microbial pathogens. Although its antimicrobial activity appeared modest under standard aerobic conditions, studies have demonstrated that hBD‐1 becomes a potent microbicidal agent under reducing conditions—effectively targeting opportunistic fungi such as "}, {"type": "i", "children": [{"type": "t", "text": "Candida albicans"}]}, {"type": "t", "text": " and anaerobic bacteria, including key commensal species ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "]."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In vivo evidence supports its protective role; for example, mice deficient in the murine ortholog of hBD‐1 exhibit delayed clearance of respiratory pathogens like "}, {"type": "i", "children": [{"type": "t", "text": "Haemophilus influenzae"}]}, {"type": "t", "text": ", underscoring its importance in maintaining epithelial barrier integrity ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "]. Moreover, genetic variations in DEFB1 have been linked to differential susceptibility to opportunistic infections in the oral cavity, where certain single‐nucleotide polymorphisms correlate with reduced Candida carriage ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "]."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n The regulation of DEFB1 expression is also finely tuned by local microenvironmental cues. In the intestinal mucosa, basal expression of DEFB1 is maintained by hypoxia‐inducible factor–1α (HIF‐1α), thereby linking oxygen tension and epithelial homeostasis to antimicrobial defense ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "]. In addition, hBD‐1 is readily detectable in colonic tissues, often in concert with other antimicrobial peptides, forming a multifaceted chemical barrier against invading microbes ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "]."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n However, pathogens have evolved countermeasures to overcome this defense. Certain bacterial virulence factors, such as the extracellular metalloprotease ZapA, can proteolytically cleave hBD‐1, leading to its inactivation and potentially contributing to immune evasion during infection ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "]. Structural analyses further highlight that, unlike related defensins that form dimers, hBD‐1 adopts a monomeric configuration, a feature that may influence both its antimicrobial potency and its interaction with microbial membranes ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ">"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "].\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings illustrate that DEFB1/hBD‐1 plays a dual role in constitutive antimicrobial defense and in shaping the host–microbe interface at epithelial barriers, while also being a target for microbial counterdefenses. This multifunctional peptide is therefore central to the maintenance of mucosal integrity and overall immune homeostasis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Bjoern O Schroeder, Zhihong Wu, Sabine Nuding, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reduction of disulphide bonds unmasks potent antimicrobial activity of human β-defensin 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature09674"}], "href": "https://doi.org/10.1038/nature09674"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21248850"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21248850"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Christian Moser, Daniel J Weiner, Elena Lysenko, et al. 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