In comparison to severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2 appears to be more contagious 1, and coronavirus disease 2019 (COVID-19) patients demonstrate varied clinical ...manifestations distinct from those seen in patients with SARS-CoV and Middle East respiratory syndrome coronavirus infections 2. Collective results from the clinical and epidemiological observations suggest a distinct viral–host interaction in COVID-19 patients. Profiling of the antibody response during SARS-CoV-2 infection may help improve our understanding of the viral–host interaction and the immunopathological mechanisms of the disease.
Humoral immune response to SARS-CoV-2 showed an early response of IgA, instead of IgM, in COVID-19 patients. As highlighted by this study, enhanced IgA responses observed in severe COVID-19 might confer damaging effects in severe COVID-19.
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•Sulfide (20 mg L−1) could reduce the specific anammox activity by 61.7%.•Protein-like substances were quenched due to sulfide stress.•Sulfide addition led Candidatus Kuenenia ...decrease while Thiobacillus increase.•Functional gene abundances significantly decreased with 20 mg L−1 sulfide.
Sulfide has attracted increasing attention due to its odor nuisance, toxicity and corrosion. Although variations in the nitrogen removal performance of anammox under sulfide stress have been reported previously, understanding the microorganisms at the molecular level is of greater significance. This study first deciphered the microbial community and functional gene response of anammox sludge to sulfide stress. Results showed that 20 mg L−1 sulfide could reduce specific anammox activity by 61.7%. The protein-like substances within extracellular polymeric substances were quenched at the end of the experiment. Moreover, the relative abundance of Candidatus Kuenenia significantly decreased from 28.7% to 6.4% while Thiobacillus increased from 0 to 7.2% due to sulfide stress. Furthermore, the abundances of functional genes (hzsA, hdh, nirK and nirS) significantly decreased when the sulfide concentration reached 20 mg L−1. These findings provide a further theoretical basis for the anammox process for nitrogen removal from wastewater containing sulfide.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Therapeutic blockade of the immune checkpoint proteins programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA4) has transformed cancer treatment. However, the overall ...response rate to these treatments is low, suggesting that immune checkpoint activation is not the only mechanism leading to dysfunctional anti-tumour immunity. Here we show that butyrophilin-like protein 2 (BTNL2) is a potent suppressor of the anti-tumour immune response. Antibody-mediated blockade of BTNL2 attenuates tumour progression in multiple in vivo murine tumour models, resulting in prolonged survival of tumour-bearing mice. Mechanistically, BTNL2 interacts with local γδ T cell populations to promote IL-17A production in the tumour microenvironment. Inhibition of BTNL2 reduces the number of tumour-infiltrating IL-17A-producing γδ T cells and myeloid-derived suppressor cells, while facilitating cytotoxic CD8
T cell accumulation. Furthermore, we find high BTNL2 expression in several human tumour samples from highly prevalent cancer types, which negatively correlates with overall patient survival. Thus, our results suggest that BTNL2 is a negative regulator of anti-tumour immunity and a potential target for cancer immunotherapy.
Microglia and oligodendrocyte precursor cells (OPCs) are critical glia subsets in the central nervous system (CNS) and are actively engaged in a body of diseases, such as stroke, Alzheimer's disease, ...multiple sclerosis, etc. Microglia and OPC serve as compelling tools for the study of CNS diseases as well as the repair and damage of myelin sheath in vitro. In this protocol, we summarized a method which is capable of using the same batch of new-born mice to isolate and culture microglia and OPCs. It integrates the characteristics of practicality, convenience, and efficiency, providing a convenient, easy, and reliable technique for research.
The feasibility of anaerobic ammonium oxidation (ANAMMOX) process to treat wastewaters containing sulfide was studied in this work. Serum bottles were used as experimental containers in batch tests ...to analyze the short-term response of the ANAMMOX process under sulfide stress. The IC50 of sulfide-S for ANAMMOX biomass was substrates-dependent and was calculated to be 264 mg L−1 at an initial total nitrogen level of 200 mg L−1 (molar ratio of ammonium and nitrite was 1:1). The long-term effects and the performance recovery under sulfide stress were continuously monitored and evaluated in an upflow anaerobic sludge blanket reactor. The performance of the ANAMMOX system was halved at an sulfide-S level of 32 mg L−1 within 13 days; however, the nitrogen removal rate (NRR) decreased by only 17.2% within 18 days at an sulfide-S concentration of 40 mg L−1 after long-time acclimatization of sludge in the presence of sulfide. The ANAMMOX performance recovered under sulfide-S level of 8 mg L−1 with a steady NRR increasing speed, linear relationship between the NRR and operation time. The synchronic reduce in the specific ANAMMOX activity and the biomass extended the apparent doubling time of the nitrogen removal capacity and decreased biomass growth rate.
► The short- and long-term effects of sulfide on ANAMMOX were distinctive. ► The changes in the properties of granule after sulfide inhibition were determined. ► The modified non-competitive inhibition model fit the batch-test data well. ► The qualitative and quantitative indicators were proposed to describe the ANAMMOX.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
Here, we review the possible reasons responsible for the occurrence, maintenance and proliferation of antibiotic resistance genes (ARGs) in the environment, as well as the corresponding mechanisms of ...their development, diffusion and transfer. Additionally, elimination strategies are also discussed. The factors that influence the development of ARGs are selection pressure, including that from antibiotics, metal and multiple other factors, co-resistance and cross-resistance, microbial consortium structure, nutrients in the environment and oxidative stress responses. Process parameters, transport pathways, and elimination strategies to reduce the health risk caused by ARGs are also reviewed in detail. Moreover, knowledge gaps and future opportunities of ARGs are addressed.
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CEKLJ, DOBA, EMUNI, FZAB, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The C-type lectin receptor Mincle is known for its important role in innate immune cells in recognizing pathogen and damage associated molecular patterns. Here we report a T cell-intrinsic role for ...Mincle in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Genomic deletion of Mincle in T cells impairs TH17, but not TH1 cell-mediated EAE, in alignment with significantly higher expression of Mincle in TH17 cells than in TH1 cells. Mechanistically, dying cells release β-glucosylceramide during inflammation, which serves as natural ligand for Mincle. Ligand engagement induces activation of the ASC-NLRP3 inflammasome, which leads to Caspase8-dependent IL-1β production and consequentially TH17 cell proliferation via an autocrine regulatory loop. Chemical inhibition of β-glucosylceramide synthesis greatly reduces inflammatory CD4+ T cells in the central nervous system and inhibits EAE progression in mice. Taken together, this study indicates that sensing of danger signals by Mincle on TH17 cells plays a critical role in promoting CNS inflammation.
Interleukin 22 (IL‐22) has an important role in colorectal tumorigenesis and many colorectal diseases such as inflammatory bowel disease and certain infections. However, the regulation of IL‐22 ...production in the intestinal system is still unclear. Here, we present evidence that butyrophilin‐like protein 2 (BTNL2) is required for colorectal IL‐22 production, and BTNL2 knockout mice show decreased colonic tumorigenesis and more severe colitis phenotypes than control mice due to defective production of IL‐22. Mechanistically, BTNL2 acts on group 3 innate lymphoid cells (ILC3s), CD4+ T cells, and γδ T cells to promote the production of IL‐22. Importantly, we find that a monoclonal antibody against BTNL2 attenuates colorectal tumorigenesis in mice and that the mBTNL2‐Fc recombinant protein has a therapeutic effect in a dextran sulfate sodium (DSS)‐induced colitis model. This study not only identifies a regulatory mechanism of IL‐22 production in the colorectal system but also provides a potential therapeutic target for the treatment of human colorectal cancer and inflammatory bowel diseases.
Synopsis
BTNL2 promotes colonic tumorigenesis in mice by regulating colorectal IL‐22 production, while it has a protective role against severe colitis. A monoclonal antibody against BTNL2 attenuates colorectal tumorigenesis.
BTNL2 is required for colorectal IL‐22 production.
BTNL2‐knockout mice show decreased colonic tumorigenesis and more severe colitis.
A monoclonal antibody against BTNL2 attenuates colorectal tumorigenesis in mice.
The mBTNL2‐Fc recombinant protein has a therapeutic effect in a DSS‐induced colitis model.
BTNL2 promotes colonic tumorigenesis in mice by regulating colorectal IL‐22 production, while it has a protective role against severe colitis. A monoclonal antibody against BTNL2 attenuates colorectal tumorigenesis.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Anaerobic ammonium oxidation (anammox) is a promising biological nitrogen removal process, due to its advantages of high efficiency and low cost. However, problems remain in the application, such as ...long startup period and susceptibility to environmental variations. Quorum sensing (QS), as a means of bacterial communication, attracts more attentions in regulating aggregation behavior and microbial density. Many physiological characteristics of anammox bacteria have been confirmed to be associated with QS, including specific anammox activity, growth rate and the production of extracellular polymeric substances (EPS), which directly affect the performance of anammox process. Therefore, a comprehensive understanding of the QS in anammox process is prerequisite. This work systematically reviewed the role and application of QS in the anammox process with the focus on mechanism. Additionally, current challenges and research needs were proposed.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
The TAGAP gene locus has been linked to several infectious diseases or autoimmune diseases, including candidemia and multiple sclerosis. While previous studies have described a role of TAGAP in T ...cells, much less is known about its function in other cell types. Here we report that TAGAP is required for Dectin-induced anti-fungal signaling and proinflammatory cytokine production in myeloid cells. Following stimulation with Dectin ligands, TAGAP is phosphorylated by EPHB2 at tyrosine 310, which bridges proximal Dectin-induced EPHB2 activity to downstream CARD9-mediated signaling pathways. During Candida albicans infection, mice lacking TAGAP mount defective immune responses, impaired Th17 cell differentiation, and higher fungal burden. Similarly, in experimental autoimmune encephalomyelitis model of multiple sclerosis, TAGAP deficient mice develop significantly attenuated disease. In summary, we report that TAGAP plays an important role in linking Dectin-induced signaling to the promotion of effective T helper cell immune responses, during both anti-fungal host defense and autoimmunity.
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