IgA Complexes Induce Neutrophil Extracellular Trap Formation More Potently Than IgG Complexes

Neutrophil extracellular trap (NET) formation is a powerful instrument to fight pathogens, but may induce collateral damage in the affected tissues. Besides pathogen-derived factors, immune complexes are potent inducers of NET formation. Neutrophils express IgA and IgG specific Fc receptors (FcRs) and therefore respond to complexed IgA and IgG. Especially in the context of autoimmune diseases, IgA and IgG immune complexes have been shown to trigger NET formation, a process that putatively contributes to disease severity. However, it is of question if both antibody classes stimulate neutrophils to the same extent. In this study, we compared the capability of IgA and IgG complexes formed by heat aggregation to induce NET formation. While stimulation of neutrophils with IgA complexes robustly induced NET formation, complexed IgG only marginally increased the amount of NETs compared to the unstimulated control. Mixing IgA with IgG before heat aggregation did not increase the effect of complexed IgA on neutrophils. By contrast, the presence of IgG complexes seemed to disturb neutrophil stimulation by IgA complexes. The capacity of complexed IgG to induce NET formation could not be increased by the addition of autologous serum or the removal of terminal sialic acid in the Fc glycan. Together, our data show that IgA is a much more potent inducer of NET formation than IgG. IgA may thus be the main driving force in (auto)immune complex-mediated NET formation.

Distribution and Evolutionary History of Sialic Acid Catabolism in the Phylum Actinobacteria

Sialic acids play essential roles in the physiology of humans and other metazoan animals, and microbial sialic acid catabolism (SAC) is one of the processes critical for pathogenesis. To date, microbial SAC is studied mainly in commensals and pathogens, while its distribution in free-living microbes and evolutionary pathway remain largely unexplored.

Host tp53 mutation induces gut dysbiosis eliciting inflammation through disturbed sialic acid metabolism

Background Host tp53 mutations are frequently found during the early stages of colitis-associated colorectal cancer (CAC), but whether such mutations induce gut microbiota dysbiosis and chronic intestinal inflammation that contributes to the development of CAC, remains unknown. Results We found that zebrafish tp53 mutant larvae exhibited elevated intestinal inflammation, by monitoring the NFκB activity in the mid-distal intestines of zebrafish larvae using an NFκB:EGFP transgenic reporter line in vivo as well as neutrophil infiltration into the intestine. This inflammation was due to dysbiotic gut microbiota with reduced diversity, revealed using both 16S rRNA amplicon sequencing and a germfree larva model. In this dysbiosis, Aeromonas spp. were aberrantly enriched as major pathobionts and exhibited the capacity for aggressive colonization in tp53 mutants. Importantly, the ex-germfree experiments supported the causality of the host tp53 mutation for inducing the inflammation. Transcriptome and high-performance liquid chromatography analyses of the host gastrointestinal tracts identified dysregulated sialic acid (SA) metabolism concomitant with increased host Neu5Gc levels as the key determinant of aberrant inflammation, which was reversed by the sialidase inhibitors oseltamivir and Philippin A. Conclusions These results demonstrate a crucial role for host tp53 in maintaining symbiosis and immune homeostasis via SA metabolism. Disturbed SA metabolism via a tp53 mutation may be exploited by specific elements of the gut microbiome, eliciting both dysbiosis and inflammation. Manipulating sialometabolism may therefore provide an efficacious therapeutic strategy for tp53 mutation-induced dysbiosis, inflammation, and ultimately, related cancers.

Synthesis of sialic acid conjugates of the clinical near-infrared dye as next-generation theranostics for cancer phototherapy

Cancer is a multifaceted global health problem that requires continuous action to develop next-generation cancer theranostics. Inspired by the emerging use of indocyanine green (ICG), the only clinical approved near-infrared...

A Study on the Skin Whitening Activity of Digesta from Edible Bird’s Nest: A Mucin Glycoprotein

Edible bird’s nest (EBN) is an unusual mucin glycoprotein. In China, it is popular among consumers due to its skin whitening activity. However, the relationship between protein, sialic acid, and the whitening activity of EBN after digestion is still unclear. In the present work, the whitening activity (antioxidant activity and tyrosinase inhibitory activity) of digested EBN were studied by HepG2 and B16 cell models. The dissolution rate of protein and sialic acid was 49.59% and 46.45% after the simulated digestion, respectively. The contents of free sialic acid and glycan sialic acid in EBN digesta were 17.82% and 12.24%, respectively. HepG2 cell experiment showed that the digested EBN had significant antioxidant activity, with EC50 of 1.84 mg/mL, and had a protective effect on H2O2-induced oxidative damage cells. The results of H2O2-induced oxidative damage showed that the cell survival rate increased from 40% to 57.37% when the concentration of digested EBN was 1 mg/mL. The results of the B16 cell experiment showed that the digested EBN had a significant inhibitory effect on tyrosinase activity, and the EC50 value of tyrosinase activity was 7.22 mg/mL. Cell experiments showed that free sialic acid had stronger antioxidant activity and tyrosinase inhibitory activity than glycan sialic acid. The contribution rate analysis showed that protein component was the main antioxidant component in digestive products, and the contribution rate was 85.87%; free sialic acid was the main component that inhibited tyrosinase activity, accounting for 63.43%. The products of the complete digestion of EBN are suitable for the development of a new generation of whitening health products.

Sialic Acid Ameliorates Cognitive Deficits by Reducing Amyloid Deposition, Nerve Fiber Production, and Neuronal Apoptosis in a Mice Model of Alzheimer’s Disease

(1) Background: As a natural carbohydrate, sialic acid (SA) is helpful for brain development, cognitive ability, and the nervous system, but there are few reports about the effect of SA on Alzheimer’s disease (AD). (2) Method: The present study evaluated the effect of SA on cognitive ability, neuronal activity, Aβ formation, and tau hyperphosphorylation in a double transgenic AD (2×Tg-AD) mice model. The 2×Tg-AD mice were randomly divided into four groups: the AD control group, 17 mg/kg SA-treated AD group, 84 mg/kg SA-treated AD group, and 420 mg/kg SA-treated AD group. Mice from all four groups were fed to 7 months of age for the behavioral test and to 9 months of age for the pathological factors investigation. (3) Results: In the Morris water maze, the escape latency significantly decreased on the fifth day in the SA-treated groups. The number of rearing and crossing times in the open field test also increased significantly, compared with the control group. SA treatment significantly reduced amyloid β-peptide (Aβ) and nerve fibers and increased the number of Nissl bodies in the brain of AD mice. (4) Conclusions: SA reduced the neuron damage by reducing Aβ and inhibited tau protein hyperphosphorylation, which improved the cognitive ability and mobility of AD mice.

Identification of Hemagglutinin Mutations Caused by Neuraminidase Antibody Pressure

HA binds with the sialic acid receptor on the host cell and initiates the infection mode of influenza virus. NA cleaves the connection between receptor and HA of newborn virus at the end of viral production.