A teleost mannose receptor with dual carbohydrate recognition domains bridges innate immunity and gut microbiota homeostasis in largemouth bass.

Abstract

Mannose receptors (MRs) are crucial pattern recognition receptors in innate immunity, yet their functional roles in teleost fish, particularly regarding systemic defense and gut microbiota regulation, remain poorly understood. In this study, we identified and characterized MsMR, a novel dual-carbohydrate recognition domain (CRD) MR from largemouth bass (Micropterus salmoides). MsMR exhibited broad-spectrum, Ca2+-dependent binding and agglutination activity against diverse bacteria and fungi, with the full-length protein showing superior functionality compared to individual CRDs. As an effective opsonin, recombinant MsMR (rMsMR) significantly enhanced phagocytosis and encapsulation of Aeromonas veronii by head kidney leukocytes. In vivo, low-dose rMsMR pretreatment showed a trend toward protection against A. veronii challenge, with mortality reduced from 55% to 25%, along with decreased bacterial loads in liver and spleen and mitigated tissue damage. This protection was associated with balanced immune responses, including downregulation of pro-inflammatory cytokines (tnf-α, il-1β) and mitigation of oxidative stress. Transcriptomic analysis revealed that MsMR is associated with coordinated activation of innate immune pathways (C-type lectin, Toll-like receptor signaling) while fine-tuning inflammation. Notably, MsMR was secreted into the intestinal lumen and shaped gut microbiota composition in a concentration-dependent manner. Our findings establish MsMR may contribute to bridge systemic antibacterial defense and gut microecological homeostasis, highlighting its potential for novel immunoprophylactic strategies in aquaculture.