Extracellular redox regulation in Pacific oyster mucosal immunity and microbiota homeostasis

Oxidation–reduction (redox) reactions are fundamental to life, regulating critical cellular processes and underpinning host defense. However, how extracellular redox homeostasis modulates invertebrate mucosal immunity remains incompletely understood. This study reveals that in the Pacific oyster ( Magallana gigas ), pathogen stimulation, including Vibrio ZJ51 and OsHV-1, significantly upregulates the expression of key redox regulatory proteins, such as thioredoxin (Trx) and glutaredoxin (Grx) in mucus. Meanwhile, a mucosa-specific defensin, Mg -Defm, was discovered as a key effector in oyster mucosa. Mg -Defm contains conserved cysteine residues forming disulfide bond. DTT treatment induced conformational changes consistent with disulfide bond reduction and was associated with a 5- to 6-fold increase in bactericidal activity against Vibrio species, suggesting that the redox state of Mg -Defm may modulate its antimicrobial activity. The upregulated multiple redox regulators in the mucosal system possibly form an extracellular switch to activate Mg -Defm. Consistent with this, both pathogenic infection and chemically induced reduction (via DTT) triggered profound microbial dysbiosis. Based on these findings, we propose that pathogen infection may alter the extracellular redox microenvironment of the oyster mucosa, potentially modulating the activity of the mucosa-specific defensin Mg -Defm. This study supports a potential role for extracellular redox regulation in invertebrate mucosal immunity and provides new insights into the maintenance of host–microbiota homeostasis.