Mannose Receptor Ligands Regulate the Gene Expression of Toll-like Receptors in Chicken Monocytes

AbstractWhen obesity arises, adipose tissue (AT) expands and shifts to an influx of pro-inflammatory cells, leading to a state of chronic AT-inflammation.Furthermore, a western diet (WD) modulates the gut microbiome, increasing intestinal permeability. This facilitates the translocation of endotoxins and even entire bacteria into the blood stream, further contributing to the pro-inflammatory state. Even though it is evident a WD, high in fat and carbohydrates (CHO), can cause AT-inflammation, it is still unclear if fat or CHO is the main inducer. Therefore, we are currently investigating the effect of different CHO-types on AT-inflammation.During 15 weeks, male C57BL/6JRj mice were kept on several diets, consisting of high-fructose (HFRD), high-sucrose-high-fructose (HCFD), high-starch (HSTD) or a WD (n = 10 per group). Weekly monitoring of body weight and food intake was followed by analyses of visceral AT-inflammation. Kruskal-wallis tests were used for statistical analysis.Mice on HSTD and HCD had gained significantly less body weight compared to mice on WD after 15 weeks of diet. Mice on HSTD also gained significantly less body weight compared to mice on HFRD and HCFD. Moreover, mice on HSTD and HCD also had significantly smaller AT-depots as compared to mice on WD. Total plasma cholesterol as well as HDL and LDL levels were significantly lower in mice on HSTD and on HCD as compared to mice on WD. Gene expression analysis revealed a significantly lower expression of several pro-inflammatory markers (F4/80, Arg1, Mannose receptor, TNF, MCP1 and Saa3) in AT of mice on HSTD and on HCD compared to a WD. A HSTD also induced lower AT-expression of MCP1 and Saa3 than a HCFD and Saa3 expression was also significantly lower in the HSTD-group compared to the HFRD-group. Furthermore, Foxp3 expression, a marker for anti-inflammatory Treg cells, was significantly increased in AT of all CHO-diet fed mice as compared to the WD-group.In conclusion, these data suggest that certain dietary carbohydrates, in contrast to a WD, do not induce obesity or AT-inflammation, including lower gene expression of Saa3. It is stated that a WD induces Saa3 expression not only in AT, but also in the colon. Furthermore, since Saa3 is able to bind bacteria and is associated with inflammation, further research is necessary to investigate Saa3 as a possible link between disturbances in the gut microbiota and AT-inflammation.

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Fumaric Acids Directly Influence Gene Expression of Neuroprotective Factors in Rodent Microglia

International Journal of Molecular Sciences ◽

10.3390/ijms20020325 ◽

2019 ◽

Vol 20 (2) ◽

pp. 325 ◽

Cited By ~ 7

Author(s):

Jessica Kronenberg ◽

Kaweh Pars ◽

Marina Brieskorn ◽

Chittappen Prajeeth ◽

Sandra Heckers ◽

...

Keyword(s):

Gene Expression ◽

Indirect Effects ◽

Protein Level ◽

Mannose Receptor ◽

Inflammatory Factors ◽

Primary Metabolite ◽

Proliferation And Differentiation ◽

Anti Inflammatory ◽

Relapsing Remitting Multiple Sclerosis

Dimethylfumarate (DMF) has been approved the for treatment of relapsing-remitting multiple sclerosis. The mode of action of DMF and its assumed active primary metabolite monomethylfumarate (MMF) is still not fully understood, notably for brain resident cells. Therefore we investigated potential direct effects of DMF and MMF on microglia and indirect effects on oligodendrocytes. Primary rat microglia were differentiated into M1-like, M2-like and M0 phenotypes and treated in vitro with DMF or MMF. The gene expression of pro-inflammatory and anti-inflammatory factors such as growth factors (IGF-1), interleukins (IL-10, IL-1β), chemokines (CCl3, CXCL-10) as well as cytokines (TGF-1β, TNFα), iNOS, and the mannose receptor (MRC1) was examined by determining their transcription level with qPCR, and on the protein level by ELISA and FACS analysis. Furthermore, microglia function was determined by phagocytosis assays and indirect effects on oligodendroglial proliferation and differentiation. DMF treatment of M0 and M1-like polarized microglia demonstrated an upregulation of gene expression for IGF-1 and MRC1, but not on the protein level. While the phagocytic activity remained unchanged, DMF and MMF treated microglia supernatants led to an enhanced proliferation of oligodendrocyte precursor cells (OPC). These results suggest that DMF has anti-inflammatory effects on microglia which may result in enhanced proliferation of OPC.

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Isolation of Murine Peritoneal Macrophages to Carry Out Gene Expression Analysis Upon Toll-like Receptors Stimulation

Journal of Visualized Experiments ◽

10.3791/52749 ◽

2015 ◽

Cited By ~ 8

Author(s):

Antonio Layoun ◽

Macha Samba ◽

Manuela M. Santos

Keyword(s):

Gene Expression ◽

Expression Analysis ◽

Gene Expression Analysis ◽

Peritoneal Macrophages ◽

Toll Like Receptors ◽

Murine Peritoneal Macrophages

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The effect of Kagocel® on gene expression of Toll-like receptors of innate immunity in THP-1 human monocytes with different levels of differentiation

BIOpreparations Prevention Diagnosis Treatment ◽

10.30895/2221-996x-2021-21-2-116-121 ◽

2021 ◽

Vol 21 (2) ◽

pp. 116-121

Author(s):

T. M. Sokolova ◽

V. V. Poloskov

Keyword(s):

Gene Expression ◽

Cell Line ◽

Active Ingredient ◽

Viral Infections ◽

Leukemia Cell ◽

Leukemia Cell Line ◽

Acute Monocytic Leukemia ◽

Toll Like Receptors ◽

Monocytic Leukemia ◽

Different Levels

Kagocel® is used in Russia for the treatment of viral infections. In terms of its chemical structure, Kagocel® active ingredient is a copolymer of gossypol polyphenol and carboxymethylcellulose. The study investigated antiviral and cytokine-inducing activity of Kagocel®, as well as its toxic effects. The aim of the study was to investigate the effect of Kagoce ® active ingredient on the induction of expression of the innate immune system receptor genes (Toll-like receptors, TLR) in the THP-1 human acute monocytic leukemia cell line with different levels of differentiation. Materials and methods: the effect of Kagocel active ingredient was investigated at the concentrations of 0.2 and 2 mg/mL in the THP-1 human acute monocytic leukemia cell line with different levels of differentiation: non-differentiated monocytes, and monocytes differentiated into macrophage-like cells. Comparative analysis of the activity of TLR 2, 3, 4, 7, 8, 9 genes was carried out by quantitative RT-PCR. The study determined standard deviations of the levels of gene expression in the experimental cells (2deltaCq ± SD) relative to the expression in the control cells. Results: Kagocel active ingredient at the concentration of 0.2 mg/mL induced activation of TLR2 expression in THP-1 monocytes by 3.5 times, TLR3 by 2 times, TLR4 by 1.6 times, and at the concentration of 2 mg/mL also induced activation of TLR7 and TLR8 by 1.4 times, and TLR9 by 2 times. The levels of TLR2, TLR3, TLR9 induction were significantly higher in THP-1 monocytes partially differentiated into macrophage-like cells, and the highest stimulation level was observed for TLR2 (8 times). Conclusions: the results obtained characterise Kagocel® as a stimulator of TLR genes in the THP-1 cell line. The number of TLR genes induced in THP-1 monocytes was shown to increase with the increase in the product concentration. THP-1 monocyte differentiation into macrophage-like cells enhances susceptibility to Kagocel®. The positive regulation of TLR genes activity may account for antiviral and interferon-inducing properties of Kagocel®, and also suggests the possibility of expanding the use of the product for various immune-associated diseases.

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SARS-CoV-2 Spike Protein Interacts with Multiple Innate Immune Receptors

10.1101/2020.07.29.227462 ◽

2020 ◽

Cited By ~ 7

Author(s):

Chao Gao ◽

Junwei Zeng ◽

Nan Jia ◽

Kathrin Stavenhagen ◽

Yasuyuki Matsumoto ◽

...

Keyword(s):

Immune Cells ◽

Mannose Receptor ◽

Innate Immune ◽

Innate Immune Cells ◽

Dependent Manner ◽

Receptor Ligands ◽

Alternative Strategies ◽

Immune Receptors ◽

Single Cell Rna Sequencing ◽

Multiple Routes

AbstractThe spike (S) glycoprotein in the envelope of SARS-CoV-2 is densely glycosylated but the functions of its glycosylation are unknown. Here we demonstrate that S is recognized in a glycan-dependent manner by multiple innate immune receptors including the mannose receptor MR/CD206, DC-SIGN/CD209, L-SIGN/CD209L, and MGL/CLEC10A/CD301. Single-cell RNA sequencing analyses indicate that such receptors are highly expressed in innate immune cells in tissues susceptible to SARS-CoV-2 infection. Binding of the above receptors to S is characterized by affinities in the picomolar range and consistent with S glycosylation analysis demonstrating a variety of N- and O-glycans as receptor ligands. These results indicate multiple routes for SARS-CoV-2 to interact with human cells and suggest alternative strategies for therapeutic intervention.

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