Insights into the tissue repair features of MAIT cells.

Mucosa-associated invariant T (MAIT) cells are a subset of innate-like non-conventional T cells characterized by multifunctionality. In addition to their well-recognized antimicrobial activity, increasing attention is being drawn towards their roles in tissue homeostasis and repair. However, the precise mechanisms underlying these functions remain incompletely understood and are still subject to ongoing exploration. Currently, it appears that the tissue localization of MAIT cells and the nature of the diseases or stimuli, whether acute or chronic, may induce a dynamic interplay between their pro-inflammatory and anti-inflammatory, or pathogenic and reparative functions. Therefore, elucidating the conditions and mechanisms of MAIT cells' reparative functions is crucial for fully maximizing their protective effects and advancing future MAIT-related therapies. In this review, we will comprehensively discuss the establishment and potential mechanisms of their tissue repair functions as well as the translational application prospects and current challenges in this field.

Microcin C7 as a Potential Antibacterial-Immunomodulatory Agent in the Postantibiotic Era: Overview of Its Bioactivity Aspects and Applications.

In the postantibiotic era, the pathogenicity and resistance of pathogens have increased, leading to an increase in intestinal inflammatory disease. Bacterial infections remain the leading cause of animal mortality. With increasing resistance to antibiotics, there has been a significant decrease in resistance to both inflammation and disease in animals, thus decreasing production efficiency and increasing production costs. These side effects have serious consequences and have detracted from the development of China's pig industry. Microcin C7 (McC7) demonstrates potent antibacterial activity against a broad spectrum of pathogens, stable physicochemical properties, and low toxicity, reducing the likelihood of resistance development. Thus, McC7 has received increasing attention as a potential clinical antibacterial and immunomodulatory agent. McC7 has the potential to serve as a new generation of antibiotic substitutes; however, its commercial applications in the livestock and poultry industry have been limited. In this review, we summarize and discuss the biosynthesis, biochemical properties, structural characteristics, mechanism of action, and immune strategies of McC7. We also describe the ability of McC7 to improve intestinal health. Our aim in this study was to provide a theoretical basis for the application of McC7 as a new feed additive or new veterinary drug in the livestock and poultry breeding industry, thus providing a new strategy for alleviating resistance through feed and mitigating drug resistance. Furthermore, this review provides insight into the new functions and anti-infection mechanisms of bacteriocin peptides and proposes crucial ideas for the research, product development, and application of bacteriocin peptides in different fields, such as the food and medical industries.

Integrated Mechanism of Immune Response Modulation by Arctium Lappa L. Fructans Based on Microbiome and Metabolomics Technologies.

Arctium lappa L. is widely consumed for its various biological effects, and polysaccharides are its main functional components. The present study aimed to evaluate the immunoregulatory effects of the main polysaccharides from burdock (ALP-1) and reveal the underlying mechanisms. ALP-1 consisted of fructose and glucose (14.57:1) and had a molecular weight of 2757 Da, with typical characteristics of (1 → 2)-linked linear fructans. Oral intake of ALP-1 significantly increased the number of colonic goblet cells, serum immunoglobulin A and immunoglobulin G levels, and fecal secretory immunoglobulin A content as well as up-regulated antioxidant enzymes and increased short chain fatty acid production. In addition, ALP-1 administration regulated pro/anti-inflammatory cytokines (i.e., interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, interferon-γ, and IL-10), intestinal microbiota structure, and the spatial information on key metabolites. Some gut-microbiota-mediated metabolic processes were also significantly altered. These results indicated that ALP-1 could exert beneficial effects on immune responses and intestinal health in healthy mice.

Coaggregated E. faecalis with F. nucleatum regulated environmental stress responses and inflammatory effects.

To investigate the cell-cell interactions of intergeneric bacterial species, the study detected the survival of Enterococcus faecalis (Ef) under monospecies or coaggregation state with Fusobacterium nucleatum subsp. polymorphum (Fnp) in environmental stress. Ef and Fnp infected the human macrophages with different forms (Ef and Fnp monospecies, Ef-Fnp coaggregates, Ef + Fnp cocultures) for exploring the immunoregulatory effects and the relevant molecular mechanisms. Meanwhile, the transcriptomic profiles of coaggregated Ef and Fnp were analyzed. Ef was shown to coaggregate with Fnp strongly in CAB within 90 min by forming multiplexes clumps. Coaggregation with Fnp reinforced Ef resistance against unfavorable conditions including alkaline, hypertonic, nutrient-starvation, and antibiotic challenges. Compared with monospecies and coculture species, the coaggregation of Ef and Fnp significantly facilitates both species to invade dTHP-1 cells and aid Ef to survive within the cells. Compared with coculture species, dual-species interaction of Ef and Fnp significantly decreased the levels of pro-inflammatory cytokines IL-6, TNF-α, and chemokines MCP-1 secreted by dTHP-1 cells and lessened the phosphorylation of p38, JNK, and p65 signaling pathways. The transcriptome sequencing results showed that 111 genes were differentially expressed or Ef-Fnp coaggregated species compared to Ef monospecies; 651 genes were differentially expressed for Fnp when coaggregation with Ef. The analysis of KEGG pathway showed that Ef differentially expressed genes (DEGs) were enriched in quorum sensing and arginine biosynthesis pathway; Fnp DEGs were differentially concentrated in lipopolysaccharide (LPS) biosynthesis, biofilm formation, and lysine degradation pathway compared to monospecies. KEY POINTS: • Coaggregated with Fnp aids Ef's survival in environmental stress, especially in root canals after endodontic treatment. • The coaggregation of Ef and Fnp may weaken the pro-inflammatory response and facilitate Ef to evade killed by macrophages. • The coaggregation between Ef and Fnp altered interspecies transcriptional profiles.

Anti-inflammatory and immunoregulatory effects of colistin sulphate on human PBMCs.

In previous studies, CST has been identified as having an immunostimulatory effect on Caenorhabditis elegans and macrophage of rats. Here, we further investigated its immunomodulatory effects on human peripheral blood mononuclear cells (PBMCs). LPS-stimulated PBMCs inflammatory model was established. Flow cytometry was applied to measure phagocytosis of PBMCs. Cytokine mRNA and protein expression levels of LPS-stimulated PBMCs with or without CST were measured by qRT-PCR and ELISA. The transcriptomic profile of CST-treated PBMCs was investigated by RNA-sequencing. Gene Ontology (GO) and Kyoto Encylopedia of Genes and Genomes (KEGG) were applied to find potential signalling pathways. PBMCs showed a significant increase in phagocytic activity at 6 h after being incubated with CST at the concentration of 10 µg/mL. In the presence of LPS, CST maintained and promoted the expression of TNF-α and chemokine CCL24. The content of pro-inflammatory cytokines, such as IL-1ß, IL-6 and IFN-γ, which were released from LPS-stimulated PBMCs, was reduced by CST at 6 h. Anti-inflammatory cytokines, such as IL-4, IL-13 and TGF-ß1, were significantly increased by CST at 24 h. A total of 277 differentially expressed immune-related genes (DEIRGs) were detected and cytokine-cytokine receptor interaction was highly enriched. CST presented obvious anti-inflammatory and immunoregulatory effects in LPS-induced PBMCs inflammatory model not only by improving the ability of PBMCs to clear pathogens but also by decreasing pro-inflammatory cytokines and increasing anti-inflammatory cytokines. And the mechanism may be related to cytokine-cytokine receptor interaction.

XiaoEr LianHuaQinqGan alleviates viral pneumonia in mice infected by influenza A and respiratory syncytial viruses.

CONTEXT: Xiaoer lianhuaqinqgan (XELH), developed based on Lianhua Qingwen (LHQW) prescription, contains 13 traditional Chinese medicines. It has completed the investigational new drug application to treat respiratory viral infections in children in China. OBJECTIVE: This study demonstrates the pharmacological effects of XELH against viral pneumonia. MATERIALS AND METHODS: The antiviral and anti-inflammatory effects of XELH were investigated in vitro using H3N2-infected A549 and LPS-stimulated RAW264.7 cells and in vivo using BALB/c mice models of influenza A virus (H3N2) and respiratory syncytial virus (RSV)-infection. Mice were divided into 7 groups (n = 20): Control, Model, LHQW (0.5 g/kg), XELH-low (2 g/kg), XELH-medium (4 g/kg), XELH-high (8 g/kg), and positive drug (20 mg/kg oseltamivir or 60 mg/kg ribavirin) groups. The anti-inflammatory effects of XELH were tested in a rat model of LPS-induced fever and a mouse model of xylene-induced ear edoema. RESULTS: In vitro, XELH inhibited the pro-inflammatory cytokines and replication of H1N1, H3N2, H1N1, FluB, H9N2, H6N2, H7N3, RSV, and HCoV-229E viruses, with (IC50 47.4, 114, 79, 250, 99.2, 170, 79, 62.5, and 93 µg/mL, respectively). In vivo, XELH reduced weight loss and lung index, inhibited viral replication and macrophage M1 polarization, ameliorated lung damage, decreased inflammatory cell infiltration and pro-inflammatory cytokines expression in lung tissues, and increased the CD4+/CD8+ ratio. XELH inhibited LPS-induced fever in rats and xylene-induced ear edoema in mice. CONCLUSION: XELH efficacy partially depends on integrated immunoregulatory effects. XELH is a promising therapeutic option against childhood respiratory viral infections.

Immunomodulation Potential of Probiotics: A Novel Strategy for Improving Livestock Health, Immunity, and Productivity.

Over the past decade, the use of probiotics as feed supplements in animal production has increased considerably due to the ban on antibiotic growth promoters in livestock. This review provides an overview of the current situation, limitation, and prospects for probiotic formulations applied to livestock. Recently, the use of probiotics in livestock has been suggested to significantly improve their health, immunity, growth performance, nutritional digestibility, and intestinal microbial balance. Furthermore, it was reported that the use of probiotics in animals was helpful in equilibrating their beneficial microbial population and microbial turnover via stimulating the host immune response through specific secretions and competitive exclusion of potentially pathogenic bacteria in the digestive tract. Recently, there has been great interest in the understanding of probiotics targeted diet and its ability to compete with harmful microbes and acquire their niches. Therefore, the present review explores the most commonly used probiotic formulations in livestock feed and their effect on animal health. In summary, this article provides an in-depth knowledge about the formulation of probiotics as a step toward a better alternative to antibiotic healthy growth strategies.

Isolation and structure elucidation of polysaccharides from fruiting bodies of mushroom Coriolus versicolor and evaluation of their immunomodulatory effects.

Coriolus versicolor is an edible medicinal mushroom in China. Two polysaccharides, named as CVPn and CVPa were separated from the dried fruiting bodies of Coriolus versicolor by water extraction and ethanol precipitation. Their chemical structures were well elucidated with overall consideration of monosaccharide composition, methylation analysis and 1D/2D-NMR spectra data. The bioactivities on RAW 264.7 macrophages cells were evaluated, and further structure-bioactivity relationships were concluded. With molecular weight of 29.7 kDa for CVPn and 50.8 kDa for CVPa, the two isolated polysaccharides were both composed of (l â†’ 4)-ß-/(1 â†’ 3)-ß-d-glucopyranosyl group as backbone with branches attached at O-6 site. Comparing to CVPn, CVPa with relative high molecular weight and less branches showed significant induction of NO production, obvious augmentation of iNOS and TNF-α mRNA expression level, and phagocytosis on RAW 264.7 cells. These results clarified that CVP polysaccharides with less branches and high molecular weight possessed enhanced immunomodulatory ability, and this finding could be a reference for the utilization of Coriolus versicolor.

Combined All-Extremity High-Intensity Interval Training Regulates Immunometabolic Responses through Toll-Like Receptor 4 Adaptors and A20 Downregulation in Obese Young Females.

Metainflammation and malfunctions of toll-like receptor 4 (TLR4) are related to obesity-induced immunometabolic morbidities. There are almost no studies relating exercise training to the TLR4 pathway and its adaptors and negative regulators. Thirty young women with obesity (exercise group and control group) were included in a 10-week all-extremity combined high-intensity interval training program. The immunomodulatory impacts of exercise on TLR4, its related adaptors (TIR domain-containing adaptor-inducing IFN-ß[TRIF], myeloid differentiation factor 88 [MyD88],and tumor receptor-associated factor 6 [TRAF6]), transcriptional factors (nuclear factor [NF]-κB and interferon regulatory factor 3 [IRF3]), and negative regulator (A20) mRNA levels were assessed by real-time PCR. Also, the serum concentration of TLR4 final products (tumor necrosis factor α [TNFα] and interferon γ [IFNγ]) was measured by ELISA. Cardiorespiratory and body composition parameters were tested, as well. There was a significant improvement in body composition and cardiorespiratory fitness. This intervention downregulated TLR4 (from 2.25 ± 1.07 to 0.84 ± 1.01), MyD88 (from 4.53 ± 5.15 to 1.27 ± 0.88), NF-κB (from 1.61 ± 2.03 to 0.23 ± 0.39), IRF3 (from 1.22 ± 0.77 to 0.25 ± 0.36), and A20 (from 0.88 ± 0.59 to 0.22 ± 0.33) levels and reduced the TNFα concentrations (from 22.39 ± 11.43 to 6.26 ± 5.31) significantly in the exercise group, while no statistically significant change was found in TRIF and TRAF6 expression and IFNγ circulating levels. It is concluded that long-term exercise modifies the inflammatory pathways and modulates the immune function at the early stages of inflammation initiation in circulating immune cells. Accordingly, we suggest time-efficient exercise protocols as a possible therapy approach for the prevention of M1 polarization.

A tolerant lactic acid bacteria, Lactobacillus paracasei, and its immunoregulatory function.

The aim of the present investigation was to isolate a probiotic strain from 23 samples of yurts cheese and 21 samples of kumiss (collected from scattered households in Xinjiang and Inner Mongolia), and from eN-Lac Capsules, a health-promoting product. The isolates were subjected to biochemical characterization analysis and were tested for tolerance to low pH, sodium salt, bile salt, pepsin, and trypsin. 16S DNA sequence analysis was conducted to identify the strain. The possible dose-dependent role of strain LP2 in immunomodulation was investigated using the ICR mouse model (from the Institute of Cancer Research). Daily, we conducted clinical observations, a carbon clearance test, a spleen lymphocyte proliferation test, and measurements of body mass and lymphoid organ index. Natural killer cell activity and delayed-type hypersensitivity reaction were determined. The results showed that 3 selected strains (LP2, LP4, and LP9) had high tolerance to low pH, sodium chloride, and bile salt and were not significantly different from Lactobacillus paracasei in terms of morphology, colony, and biochemistry characterizations. A further tolerance test showed that LP2 had the highest survival rate (90%) under the conditions of pH 3.0, 0.3% bile salt, 10 mg/mL pepsin, and 10 mg/mL trypsin for 24 h. The sequence heterogeneities within the 16S rDNA genes molecularly elucidated that the LP2 belongs to the L. paracasei family, on the basis of a homology of 99.6%. A significant enhanced footpad swelling reaction and natural killer cell activity in the middle-dose (10(8) cfu/mL) and the high-dose (10(9) cfu/mL) groups were observed but without obvious dose dependence (P < 0.05). Lymphocyte proliferation was also increased significantly in a dose-dependent manner (P < 0.01) compared with that of the control group, indicating a positive immunoregulatory effect.

Immunoregulation of icariin combined with Panax notoginseng saponins in mice / 中草药

Objective To investigate the regulatory effects of icariin (ICA) combined with the Panax notoginseng saponins (PNS) on immunological function in mice and provide some experimental evidences for the combination mechanism improving the spatial learning and memory abilities of Alzheimer's disease (AD) animal model. Methods Based on serum pharmacological method, the ICR mice were individually ig administrated with ICA+PNS [(40+320), (80+640), and (160+ 1 280 ) mg/kg] or ICA (80 mg/kg), and PNS (640 mg/kg) only for 7 d. Drug-containing serum was prepared and effects on spleen lymphocyte proliferation of Bable/c mice induced by concanavalin-A (ConA) or lipopolysaccharide (LPS) and on interleukin-2 (IL-2) secretion were observed in vitro. Meanwhile, the immunological organ indexes of treated mice were evaluated. Results Drug-containing serum of ICA+PNS [(80+640) and (160+ 1 280 ) mg/kg] could improve the spleen lymphocyte proliferation induced by ConA (P0.05). Drug-containing serum of ICA+PNS [(80+640) and (160+ 1 280) mg/kg] could improve IL-2 production (P0.05), respectively. Conclusion ICA combined with PNS could improve immunological function selectively and promote T cell function in mice.