PD-L1 negatively regulates antifungal immunity by inhibiting neutrophil release from bone marrow

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Nov. 11, 2022

Abstract Programmed death ligand 1 (PD-L1) has been shown to be inducibly expressed on neutrophils suppress host immunity during polymicrobial sepsis, virus and parasite infections. However, the role of PD-L1 neutrophil-mediated antifungal remains wholly unknown. Here, we show that expression murine human was upregulated upon engagement C-type lectin receptor Dectin-1 with its β-glucans, exposed fungal pathogen Candida albicans yeast. Moreover, β-glucan stimulation induced translocation into nucleus regulate production chemokines CXCL1 CXCL2, which control neutrophil mobilization. Importantly, C. infection-induced leads accumulation in bone marrow, through mediating their autocrine secretion CXCL1/2. Furthermore, neutrophil-specific deficiency impaired CXCL1/2 secretion, promoted migration from marrow peripheral circulation, thereby conferring resistance infection. Finally, either blockade or pharmacological inhibition significantly increased release enhance immunity. Our data together indicate activation Dectin-1/PD-L1 cascade by β-glucans inhibits reserve, contributing negative regulation innate immunity, functions as a potent immunotherapeutic target against life-threatening fungi

Language: Английский

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Neutrophil diversity and plasticity: Implications for organ transplantation

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 20(9), P. 993 - 1001

Published: June 29, 2023

Abstract Neutrophils, as the first defenders against external microbes and stimuli, are highly active finely regulated innate immune cells. Emerging evidence has challenged conventional dogma that neutrophils a homogeneous population with short lifespan promotes tissue damage. Recent findings on neutrophil diversity plasticity in homeostatic disease states have centered circulation. In contrast, comprehensive understanding of tissue-specialized health is still lacking. This article will discuss how multiomics advances contributed to our heterogeneity diversification resting pathological settings. discussion be followed by focus role solid organ transplantation may contribute transplant-related complications. The goal this provide an overview research involvement transplantation, aim draw attention underappreciated area research.

Language: Английский

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Exploring causal correlations between inflammatory cytokines and knee osteoarthritis: a two-sample Mendelian randomization

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 18, 2024

Knee osteoarthritis (KOA) and certain inflammatory cytokines (such as interleukin 1 [IL-1] tumor necrosis factor alpha [TNF-a]) are related; however, the causal relationship remains unclear. Here, we aimed to assess between 41 KOA using Mendelian randomization (MR).

Language: Английский

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Simple dysmood disorder, a mild subtype of major depression, is not an inflammatory condition: Depletion of the compensatory immunoregulatory system

Journal of Affective Disorders, Journal Year: 2025, Volume and Issue: 375, P. 75 - 85

Published: Jan. 21, 2025

Language: Английский

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Targeting the Tumor Microenvironment: A Close Up of Tumor-Associated Macrophages and Neutrophils

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: May 19, 2022

The importance of the tumor microenvironment (TME) in dynamically regulating cancer progression and influencing therapeutic outcome is widely accepted appreciated. Several strategies to modify or modulate TME, like angiogenesis immune checkpoint inhibitors, showed clinical efficacy received approval from regulatory authorities. Within recent decades, new promising targeting myeloid cells have been implemented preclinical models. predominance specific cell phenotypes TME has attributed pro- anti-tumoral. Hence, their modulation can, turn, alter responses standard-of-care treatments, making them more less effective. Here, we summarize discuss current knowledge correlated challenges about tumor-associated macrophages neutrophils strategies, future developments.

Language: Английский

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Restoring Prohealing/Remodeling-Associated M2a/c Macrophages Using ON101 Accelerates Diabetic Wound Healing

JID Innovations, Journal Year: 2022, Volume and Issue: 2(5), P. 100138 - 100138

Published: June 2, 2022

Diabetic wounds exhibit chronic inflammation and delayed tissue proliferation or remodeling, mainly owing to prolonged proinflammatory (M1) macrophage activity defects in transition prohealing/proremodeling (M2a/M2c; CD206+ and/or CD163+) macrophages. We found that topical treatment with ON101, a plant-based potential therapeutic for diabetic foot ulcers, increased M2c-like (CD163+ CD206+) cells suppressed M1-like cells, altering the inflammatory gene profile mouse model compared controls. An vitro macrophage-polarizing revealed ON101 directly CD80+ CD86+ M1-macrophage polarization M1-associated cytokines at both protein transcriptional levels. Notably, conditioned medium collected from ON101-treated M1 macrophages reversed M1-conditioned medium‒mediated suppression of Furthermore, adipocyte progenitor significantly promoted CD163+ but strongly inhibited cells. also stimulated expression GCSF CXCL3 genes human Interestingly, recombinant enhanced M2 markers, whereas only Depletion cutaneous ON101-induced wound healing. Thus, facilitated GCSF- CXCL3-mediated macrophages, lowering leading faster

Language: Английский

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Advances in cell membrane-coated nanoparticles and their applications for bone therapy

Biomaterials Advances, Journal Year: 2022, Volume and Issue: 144, P. 213232 - 213232

Published: Dec. 5, 2022

Language: Английский

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Evolution of developmental and comparative immunology in poultry: The regulators and the regulated

Developmental & Comparative Immunology, Journal Year: 2022, Volume and Issue: 138, P. 104525 - 104525

Published: Sept. 2, 2022

Avian has a unique immune system that evolved in response to environmental pressures all aspects of innate and adaptive responses, including localized circulating lymphocytes, diversity immunoglobulin repertoire, various cytokines chemokines. All these attributes make birds an indispensable vertebrate model for studying the fundamental immunological concepts comparative immunology. However, research on lags far behind humans, mice, other agricultural animal species, limited tools have hindered adequate application as disease models mammalian systems. An in-depth understanding avian relies detailed studies regulated regulatory mediators, such cell surface antigens, cytokines, Here, we review current knowledge centered roles chemokines, beyond. Moreover, provide update recent progress this rapidly developing field study with respect availability reagents will facilitate components poultry immunity. The new information immunity available benefit researchers evolutionary biologists conducting applied research.

Language: Английский

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Potential diagnostic and drug target markers in glioblastoma

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: March 27, 2024

Abstract Glioblastoma multiforme (GBM) IDH-wildtype is the most prevalent brain malignancy in adults. However, molecular mechanisms, which leads to GBM have not been completely elucidated. Granulocyte colony-stimulating factor (GCSF), receptor GCSFR, and Signal transducers activators of transcription 3 (STAT3) involved occurrence development various cancers, but their role little known. Herein, we investigated gene protein expression GCSF, STAT3 21 tissue biopsy samples also tumor associated normal (TANT) derived from glioblastoma patients, revealed significantly differential these genes. To validate our findings, performed a comprehensive integrated analysis transcriptomic proteomic profiling respective genes by retrieving RNA-sequence data Genome Atlas Databases. GO KEGG enrichment disease-related pathways, such as JAK/STAT pathway activation, were with progression. We further computational docking potential drug candidate Nisin against results validated vitro through cytotoxic activity assay using human cell line SF-767 dose-dependent manner. Our reveals that GCSF augments glioma progression, its blockade anticancer bacteriocin peptide can potentially inhibit growth metastasis GBM.

Language: Английский

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Major depressive disorder, neuroticism, suicidal behaviors, and depression severity are all associated with neurotoxic immune networks and their intricate interactions with metabolic syndrome.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: April 5, 2024

Abstract Background Major depressive disorder (MDD) is considered to be a neuroimmune disorder. However, there are no data regarding the association between comprehensive immune profiles and their interactions with metabolic syndrome (MetS) in predicting neuroticism, suicidal behaviors, severity of outpatient MDD (OMDD). Methods We assayed 48 serum cytokines, chemokines, growth factors using multiplex assay 67 healthy controls 66 OMDD patients. Around 50% control participants had diagnosis MetS. Results Ten differentially expressed proteins (DEPs) were upregulated (i.e., CXCL12, TNFB, PDGF, CCL11, IL9, IL4, CCL5, CCL2, CCL4, IL1RN), indicating an immune, defense stress response. Six DEPs downregulated (VEGFA, IL12, CCL3, CSF1, IL1B, NGF), lowered neurogenesis regulation neuron death. Significant MetS caused a) substantial increases TNF signaling, upregulation IL17, TNF, IL1RN; b) downregulation VEGFA FGF. A large part variance neuroticism (26.6%), behaviors (23.6%), phenome (31.4%) was predicted by immunological TNFB or VEGFA. Discussion characterized immunoneurotoxic profile which partly explains phenome’s severity. Lowered IL-10 increased neurotoxicity characteristics other depression phenotypes, including severe first-episode inpatient MDD. The presence considerably exacerbates immunoneurotoxicity. Consequently, studies should always performed subjects without

Language: Английский

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