Targeting Psoroptes ovis MIF to improve skin barrier function: A novel prophylactic strategy for psoroptic mange

Psoroptic mange, caused by the mite Psoroptes ovis, poses a major challenge to global livestock production, with current control strategies limited by acaricide resistance, residue issues, and environmental concerns. This underscores the need for innovative approaches targeting parasite-host interactions. While disruption of skin barrier homeostasis is recognized as a key driver in the pathogenesis of many dermatoses, its potential as a preventive target in parasitic skin diseases remains largely undefined. Herein, we investigated the role of Psoroptes ovis macrophage migration inhibitory factor (PsoMIF) in modulating the host skin barrier and evaluated its potential as a preventive target. The impact of recombinant PsoMIF (rPsoMIF) on keratinocyte barrier markers was first analyzed in vitro using HaCaT cells. Its barrier-disrupting effect was then validated in vivo in a healthy rabbit model. Finally, the prophylactic efficacy of a PsoMIF-specific antibody (PsoMIF-IgG) was assessed in a P. ovis challenge model. In vitro, rPsoMIF significantly disturbed the proliferation-differentiation balance in HaCaT cells, upregulating markers of proliferation (Ki67, K6, K5, and K14) while downregulating key terminal differentiation proteins (FLG, IVL). It also promoted the expression of inflammatory cytokines (IFN-γ, IL-4, IL-17A) and antimicrobial peptides (LL37, S100A9). In vivo, rPsoMIF injection recapitulated key pathological features of natural infestation. Crucially, PsoMIF-IgG prophylaxis in mite-challenge rabbits significantly improved clinical signs, drastically reduced mite burden and scab weight, and alleviated barrier dysfunction by ameliorating hyperplasia, modulating the proliferation-differentiation balance, and suppressing inflammation. Importantly, an in vitro acaricidal assay confirmed that PsoMIF-IgG lacks direct mite-killing activity, underscoring that its prophylactic efficacy is mediated through host-directed mechanisms. Our findings identify PsoMIF as a critical pathogenic mediator that drives skin barrier dysfunction in psoroptic mange. Targeting blockade of PsoMIF represents a novel prophylactic strategy for psoroptic mange control.