Mannose Receptor Mediates the Activation of Chitooligosaccharides on Blunt Snout Bream (Megalobrama amblycephala) Macrophages

Abstract

Chitooligosaccharide (COS) is an important immune enhancer and has been proven to have a variety of biological activities. Our previous research has established an M1 polarization mode by COS in blunt snout bream (Megalobrama amblycephala) macrophages, but the mechanism of COS activation of blunt snout bream macrophages remains unclear. In this study, we further explored the internalization mechanism and signal transduction pathway of chitooligosaccharide hexamer (COS6) in blunt snout bream macrophages. The results showed that mannose receptor C-type lectin-like domain 4-8 of M. amblycephala (MaMR CTLD4-8) could recognize and bind to COS6 and mediate COS6 into macrophages by both clathrin-dependent and caveolin-dependent pathways. In the inflammatory response of macrophages activated by COS6, the gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and nitric oxide synthase 2 (NOS2) was significantly inhibited after MaMR CTLD4-8-specific antibody blockade. However, even if it was blocked, the expression of these inflammation-related genes was still relatively upregulated, which suggested that there are other receptors involved in immune regulation. Further studies indicated that MaMR CTLD4-8 and Toll-like receptor 4 (TLR4) cooperated to regulate the pro-inflammatory response of macrophages caused by COS6. Taken together, these results revealed that mannose receptor (MR) CTLD4-8 is indispensable in the process of recognition, binding, internalization, and immunoregulation of COS in macrophages of blunt snout bream.

The Effect of N-Acetylation on the Anti-Inflammatory Activity of Chitooligosaccharides and Its Potential for Relieving Endotoxemia

“…COS has smaller molecular weight (MW), lower degree of polymerization (DP), and good water solubility which chitosan does not possess [ 13 , 14 , 15 ]. Similar to other natural carbohydrate [ 16 , 17 ], COS has been shown to have good immunogenicity and anti-inflammatory activity in vitro [ 18 , 19 , 20 ] and in vivo [ 21 , 22 , 23 ], and is expected to be a good natural anti-inflammatory drug to prevent and treat endotoxemia. The anti-inflammatory activity of COS is related to its structural parameters, including MW, DP and degree of acetylation (DA) etc.…”

Oral Administration of Nanopeptide CMCS-20H Conspicuously Boosts Immunity and Precautionary Effect Against Bacterial Infection in Fish

“…Immunopotentiators, based on recent successes in both laboratory and clinic, are considered a viable option for controlling bacterial diseases ( 9 , 10 ). Some antimicrobial peptides (AMPs) have good immune regulation function, so they can also be used as immunopotentiators.…”

Pleiotropic Modulation of Chitooligosaccharides on Inflammatory Signaling in LPS-Induced Macrophages

“…They also proved that the internalization of COS depends on the mannose receptor to some extent [ 33 ]. Aotian Ouyang et al systematically explored the mechanism of action of mannose receptors (MR) in COS internalization and concluded that MR and TLR4 act synergistically, although they used blunt-snout-bream macrophages [ 15 ]. Although MR has been studied more frequently, COS can still be internalized and show its activity after the inhibition of the MR, which is consistent with the increased expression of multiple receptors in the RNA-seq results.…”

“…Furthermore, COS can alleviate enteritis damage in mice or turbot [ 13 , 14 ]. There is also some research suggesting that COS could modulate macrophage polarization in mice or blunt-snout bream [ 15 , 16 ]. Our previous work demonstrated the anti-inflammatory activity of COS in vitro and in vivo and found that COS with a degree of acetylation (DA) = 12% was the best.…”