{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Human alpha‐defensin 1 (DEFA1), which encodes neutrophil peptide 1 (HNP‐1), is emerging as a key effector molecule in innate host defense with multiple roles spanning direct antimicrobial activity, immunomodulation, and potential utility as a disease biomarker. DEFA1 is produced predominantly by neutrophils and Paneth cells, where it is initially synthesized as an inactive precursor that is activated by proteases such as matrix metalloproteinase‐7; once activated, its ability to form membrane pores facilitates broad‐spectrum killing of microbes and parasites by disrupting membrane integrity (see, for example."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition to its direct microbicidal function, DEFA1 has been shown to stimulate pro‐inflammatory cytokine release (notably interleukin‐6) from macrophages, thereby linking antimicrobial action with downstream immune signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Structural and genetic studies highlight that DEFA1 exhibits extensive copy number variation—an observation that correlates with differences in mRNA expression levels and influences susceptibility to inflammatory disorders such as severe sepsis and coronary heart disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": " Detailed structure–function investigations using solid‐state NMR have resolved key features of HNP‐1, elucidating how its conformation underpins potent interactions with microbial membranes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, experimental models using epithelial cells demonstrate that DEFA1 secretion can limit parasite motility and invasion—for instance, by impairing Trypanosoma cruzi infectivity through flagellar disruption."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, aberrant DEFA1 expression in diverse tissues—including altered levels in salivary gland tumors—further suggests a role beyond direct microbial killing, potentially informing on immune‐mediated neoplastic processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Collectively, these findings underscore the multifaceted function of DEFA1 as both an antimicrobial agent and an immunomodulatory molecule whose genetic variability and expression patterns may serve as important biomarkers in inflammatory and infectious diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "R E Vandenbroucke, I Vanlaere, F Van Hauwermeiren, et al. 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