A novel calreticulin of Psoroptes ovis regulated keratinocyte function resulting in host skin barrier dysfunction: implications for involvement in the pathogenesis of psoroptic mange.

Abstract

Background: Psoroptes ovis, the causative agent of psoroptic mange, affects a wide range of domestic and wild animals, causing substantial economic losses and threatening wildlife survival. However, the underlying pathogenesis of this ectoparasitic disease remains poorly understood.

Methods: In this study, we comprehensively characterized the sequence conservation and excretory-secretory properties of P. ovis calreticulin (PsoCRT) using sequence alignment, immunoblotting, and immunofluorescence assays. To investigate the functional impact of recombinant PsoCRT (rPsoCRT), we conducted in vitro studies assessing its effects on keratinocyte proliferation, migration, differentiation, and the expression of immune regulatory factors. In addition, we employed rabbit ear intradermal injections of rPsoCRT to histologically observe tissue changes and confirm alterations in the expression profiles of immune regulatory factors.

Results: PsoCRT was expressed across all developmental stages of P. ovis, with peak expression observed in adult males. Notably, PsoCRT was excreted and secreted into the host epidermis, primarily localizing within the stratum granulosum and spinosum. Intriguingly, sera from rabbits infested with P. ovis did not recognize PsoCRT. In vitro studies revealed that rPsoCRT significantly inhibited keratinocyte proliferation and migration, promoted differentiation, and upregulated the expression of interleukin (IL)-1β, IL-6, IL-36, C-C motif chemokine ligand 27 (CCL27), and vascular endothelial growth factor (VEGF) in vitro, without altering the levels of interferon (IFN)-γ or tumor necrosis factor (TNF)-α. In vivo, rabbit ear intradermal injections of rPsoCRT induced epidermal cell differentiation, immune cell infiltration, and an upregulation of IL-6, CCL27, and VEGF expression.

Conclusions: PsoCRT disrupted the physical and immune barriers of keratinocytes, leading to skin dysfunction and facilitating a microenvironment conducive to P. ovis parasitization, thereby highlighting its important role in the pathogenesis of psoroptic mange.