المؤلفون: Yun Zhou, Craig McClain, Wenke Feng

المصدر: Applied Microbiology, Vol 4, Iss 2, Pp 620-634 (2024)

مصطلحات موضوعية: alcohol-associated liver disease, P. gingivalis, inflammatory monocyte infiltration, intrahepatic neutrophil infiltration, hepatic steatosis, liver injury, Microbiology, QR1-502

الوصف: The liver plays a vital role in the defense against infections. Porphyromonas gingivalis (P. gingivalis), a dominant etiologic oral bacterium implicated in periodontal disease (PD), has been associated with various systemic diseases. This study aimed to investigate the influence of P. gingivalis on alcohol-associated liver diseases (ALD). Mice were fed a Lieber–DeCarli liquid diet containing 5% ethanol for 10 days after an initial adaptation period on a diet with lower ethanol content for 7 days. Two days before tissue sample collection, the mice were administered P. gingivalis strain W83 (Pg) through intraperitoneal injection (IP). Pair-fed mice with Pg infection (PF+Pg) exhibited an activated immune response to combat infections. However, alcohol-fed mice with Pg infection (AF+Pg) showed liver injury with noticeable abscess lesions and elevated serum alanine aminotransferase (ALT) levels. Additionally, these mice displayed liver infiltration of inflammatory monocytes and significant downregulation of proinflammatory cytokine gene expression levels; and AF+Pg mice also demonstrated increased intrahepatic neutrophil infiltration, as confirmed by chloroacetate esterase (CAE) staining, along with elevated gene expression levels of neutrophil cytosol factor 1 (Ncf1), neutrophilic inflammation driver lipocalin 2 (Lcn2), and complement component C5a receptor 1 (C5ar1), which are associated with neutrophilic inflammation. Interestingly, compared to PF+Pg mice, the livers of AF+Pg mice exhibited downregulation of gene expression levels of NADPH oxidase 2 (Cybb), the leukocyte adhesion molecule Cd18, and the Toll-like receptor adaptor Myd88. Consequently, impaired clearance of P. gingivalis and other bacteria in the liver, increased susceptibility to infections, and inflammation-associated hepatic necrotic cell death were observed in AF+Pg mice, which is likely to have facilitated immune cell infiltration and contributed to liver injury. Furthermore, in addition to the Srebf1/Fasn pathway induced by alcohol feeding, Pg infection also activated carbohydrate response element-binding protein (ChREBP) in AF+Pg mice. In summary, this study demonstrates that P. gingivalis infection, acting as a “second hit”, induces dysfunction of immune response and impairs the clearance of bacteria and infections in alcohol-sensitized livers. This process drives the development of liver injury.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2673-8007/4/2/43Test; https://doaj.org/toc/2673-8007Test

الوصول الحر: https://doaj.org/article/0da390a238384981b9557decf3d27cecTest

المؤلفون: Kang Tang, Yongli Hou, Linfeng Cheng, Yusi Zhang, Juan Li, Qi Qin, Xuyang Zheng, Xiaozhou Jia, Chunmei Zhang, Ran Zhuang, Yun Zhang, Boquan Jin, Lihua Chen, Ying Ma

المصدر: Annals of Medicine, Vol 55, Iss 2 (2023)

مصطلحات موضوعية: Hantaan virus, hemorrhagic fever with renal syndrome, inflammatory monocyte, CD226, antigen presentation, Medicine

الوصف: AbstractBackground Hantaan virus (HTNV) infection can cause severe hemorrhagic fever with renal syndrome (HFRS). Inflammatory monocytes (iMOs) are involved in early antiviral responses. Previous studies have found that blood iMOs numbers increase in the acute phase of HFRS. Here, we further identified the phenotypic characteristics of iMOs in HFRS and explored whether phenotypic changes in iMOs were associated with HFRS severity.Materials and Methods Blood samples from 85 HFRS patients were used for phenotypic analysis of iMOs by flow cytometry. Plasma HTNV load was determined using RT-PCR. THP-1 cells overexpressing CD226 were used to investigate the effects of CD226 on HLA-DR/DP/DQ and CD80 expression. A mouse model was used to test macrophage phenotype following HTNV infection.Results The proportion of CD226- iMOs in the acute phase of HFRS was 66.83 (35.05-81.72) %, which was significantly higher than that in the convalescent phase (5.32 (1.36-13.52) %) and normal controls (7.39 (1.15-18.11) %) (p

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/0785-3890Test; https://doaj.org/toc/1365-2060Test

الوصول الحر: https://doaj.org/article/6155cebc8f36424fa64f977a3e097013Test

المؤلفون: Zhaoyue Fu, Yongli Hou, Håvard Jostein Haugen, Xutao Chen, Kang Tang, Liang Fang, Yong Liu, Shu Zhang, Qianli Ma, Lihua Chen

المصدر: Journal of Nanobiotechnology, Vol 21, Iss 1, Pp 1-16 (2023)

مصطلحات موضوعية: TiO2, Cytoskeleton, Inflammatory monocyte (iMos), Simulated microgravity (SMG), Macrophage polarization, Biotechnology, TP248.13-248.65, Medical technology, R855-855.5

الوصف: Abstract Background Microgravity directly disturbs the reorganization of the cytoskeleton, exerting profound effects on the physiological process of macrophages. Although it has been established that macrophage M1/M2 polarization could be manipulated by the surface nanostructure of biomaterial in our previous study under normal gravity, how will inflammatory monocytes (iMos)-derived macrophages respond to diverse nanostructured Ti surfaces under normal gravity or microgravity remains unrevealed. Results In this study, Cytochalasin D, a cytoskeleton relaxant, was employed to establish the simulated microgravity (SMG) environment. Our results showed that human iMos polarized into M2c macrophages on NT5 surface but M1 type on NT20 surface with divergent inflammatory phenotypes according to the profile of macrophage polarization featured molecules under normal gravity. However, such manipulative effects of NTs surfaces on iMos-derived macrophages were strikingly weakened by SMG, characterized by the altered macrophage morphology, changed cytokine secretion profile, and decreased cell polarization capacity. Conclusions To our knowledge, this is the first metallic implantable material study focusing on the functions of specific monocyte subsets and its crucial role of the cytoskeleton in materials-mediated host immune response, which enriches our mechanism knowledge about the crosstalk between immunocytes and biomaterials. The results obtained in the present study may also provide potential targets and strategies for biomaterial development and clinical treatment via precise immune-regulation under normal gravity and microgravity. Graphic Abstract

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1477-3155Test

الوصول الحر: https://doaj.org/article/99489b9b5ecf41478d99c1813297ce7aTest

المؤلفون: Charles L. Howe, Reghann G. LaFrance-Corey, Brittany L. Overlee, Renee K. Johnson, Benjamin D. S. Clarkson, Emma N. Goddery

المصدر: Journal of Neuroinflammation, Vol 19, Iss 1, Pp 1-19 (2022)

مصطلحات موضوعية: Theiler’s murine encephalomyelitis virus, Inflammatory monocyte, Microglia, Viral encephalitis, Hippocampus, Seizure, Neurology. Diseases of the nervous system, RC346-429

الوصف: Abstract Background The pathogenic contribution of neuroinflammation to ictogenesis and epilepsy may provide a therapeutic target for reduction of seizure burden in patients that are currently underserved by traditional anti-seizure medications. The Theiler's murine encephalomyelitis virus (TMEV) model has provided important insights into the role of inflammation in ictogenesis, but questions remain regarding the relative contribution of microglia and inflammatory monocytes in this model. Methods Female C57BL/6 mice were inoculated by intracranial injection of 2 × 105, 5 × 104, 1.25 × 104, or 3.125 × 103 plaque-forming units (PFU) of the Daniel’s strain of TMEV at 4–6 weeks of age. Infiltration of inflammatory monocytes, microglial activation, and cytokine production were measured at 24 h post-infection (hpi). Viral load, hippocampal injury, cognitive performance, and seizure burden were assessed at several timepoints. Results The intensity of inflammatory infiltration and the extent of hippocampal injury induced during TMEV encephalitis scaled with the amount of infectious virus in the initial inoculum. Cognitive performance was preserved in mice inoculated with 1.25 × 104 PFU TMEV relative to 2 × 105 PFU TMEV, but peak viral load at 72 hpi was equivalent between the inocula. CCL2 production in the brain was attenuated by 90% and TNFα and IL6 production was absent in mice inoculated with 1.25 × 104 PFU TMEV. Acute infiltration of inflammatory monocytes was attenuated by more than 80% in mice inoculated with 1.25 × 104 PFU TMEV relative to 2 × 105 PFU TMEV but microglial activation was equivalent between groups. Seizure burden was attenuated and the threshold to kainic acid-induced seizures was higher in mice inoculated with 1.25 × 104 PFU TMEV but low-level behavioral seizures persisted and the EEG exhibited reduced but detectable abnormalities. Conclusions The size of the inflammatory monocyte response induced by TMEV scales with the amount of infectious virus in the initial inoculum, despite the development of equivalent peak infectious viral load. In contrast, the microglial response does not scale with the inoculum, as microglial hyper-ramification and increased Iba-1 expression were evident in mice inoculated with either 1.25 × 104 or 2 × 105 PFU TMEV. Inoculation conditions that drive inflammatory monocyte infiltration resulted in robust behavioral seizures and EEG abnormalities, but the low inoculum condition, associated with only microglial activation, drove a more subtle seizure and EEG phenotype.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1742-2094Test

الوصول الحر: https://doaj.org/article/36d646d746d34492ad1f55df48b32c7dTest

المؤلفون: E. V. Shikh, N. A. Petunina, L. V. Nedosugova, K. O. Galstyan, K. I. Kolmychkova, A. A. Makhova, Galin I. Gorodetskaya

المصدر: Сахарный диабет, Vol 23, Iss 3, Pp 210-222 (2020)

مصطلحات موضوعية: type 2 diabetes mellitus, diabetic foot syndrome (dfs), pro-inflammatory monocyte polarization, anti-inflammatory monocyte polarization, kokarnite, Nutritional diseases. Deficiency diseases, RC620-627

الوصف: AIMS: Investigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and the anti-inflammatory chemokine C-C Motif Chemokine Ligand 18 (CCL18) by monocytes isolated from blood of patients with long-term type 2 diabetes mellitus (T2DM), both with or without foot ulcers and the effect of the course use of the combined metabolic drug Kokarnit as part of complex therapy on the dynamics of the severity of symptoms of DSPN and the cytokine phenotype in patients with long-term non-healing ulcers of the lower extremities MATERIALS AND METHODS: 121 patients with T2DM, 79 without diabetic foot syndrome (DFS) and 42 patients with DFS were included. CD14+ monocytes were isolated from patients’ blood and stimulated by interferon-γ (IFN-γ) and interleukine-4 (IL-4) for induction of pro- and anti-inflammatory monocyte activation, respectively. The concentrations of TNF-α and CCL18 in the culture medium were measured using ELISA on day 1 and day 6 after cell stimulation in all patients before taking the combined metabolic drug Kokarnit. Then they were randomly allocated either to the control group (57 people), to whom Kokarnit was added to standard treatment, or to the comparison group. After a 9-day course of application of Kokarnit, the dynamics of indicators was evaluated on a TSS scale. Assessment of cytokine status was carried out in 18 people with long-term non-healing ulcerative defects of the lower extremities, on the first and ninth day of treatment. RESULTS: A correlation was found between HbA1c and levels of stimulated secretion of TNFα (r=0.726, p=0.027), CCL18 (r=-0.949, p=0.051) in patients with DSPN. In all patients with different duration of VDS, an increase in secretion of TNF-α and CCL18 was observed (p

وصف الملف: electronic resource

العلاقة: https://www.dia-endojournals.ru/jour/article/view/12343Test; https://doaj.org/toc/2072-0351Test; https://doaj.org/toc/2072-0378Test

الوصول الحر: https://doaj.org/article/88cb4542a9cf40a9a169a550921c30c7Test

المؤلفون: Mabel Toribio (14312262), Magid Awadalla (6393887), Zsofia D. Drobni (12369154), Thiago Quinaglia (7232720), Melissa Wang (2132755), Claudia G. Durbin (9037494), David A. Alagpulinsa (14312265), Lindsay T. Fourman (14312268), Giselle Alexandra Suero-Abreu (14312271), Michael D. Nelson (9727972), Takara L. Stanley (14312274), Christopher T. Longenecker (5029295), Tricia H. Burdo (9592101), Tomas G. Neilan (5571194), Markella V. Zanni (8562825)

مصطلحات موضوعية: Medicine, Cell Biology, Biotechnology, Evolutionary Biology, Immunology, Developmental Biology, Cancer, Infectious Diseases, Virology, Computational Biology, +women%22">xlink "> women, monocytes (&# 961, face heightened risks, determine whether targeting, 4 &# 177, +wwh%22">xlink "> wwh, women without hiv, lv systolic function, inflammatory monocyte activation, 9 %, 1 &# 177, lower among women, lower gls compared, among 20 wwh, monocyte activation, lower gls, among wwh, wwh vs, whole group

الوصف: Additional details on the assessment of global longitudinal strain using cardiovascular MRI can be found in our Supplemental Methods. (DOCX)

العلاقة: https://figshare.com/articles/journal_contribution/Global_longitudinal_strain_supplemental_methods_/21797643Test

الإتاحة: https://doi.org/10.1371/journal.pone.0279913.s002Test

المؤلفون: Charles L. Howe (11880660), Reghann G. LaFrance-Corey (12019095), Brittany L. Overlee (12019098), Renee K. Johnson (12019101), Benjamin D. S. Clarkson (12019104), Emma N. Goddery (11353986)

مصطلحات موضوعية: Medicine, Microbiology, Neuroscience, Pharmacology, Immunology, Infectious Diseases, Plant Biology, Virology, Biological Sciences not elsewhere classified, Theiler’s murine encephalomyelitis virus, Inflammatory monocyte, Microglia, Viral encephalitis, Hippocampus, Seizure, Epilepsy, Neuroinflammation

الوصف: Additional file 1: Fig. S1. Gating strategy for brain-infiltrating leukocyte analyses. Singlets are further refined by GFP intensity or CD45-positivity and then sub-gated on Gr1 or 1A8 and CD11b. Cells that are GFP bright are Gr1-positive and 1A8-positive neutrophils, while cells that are GFP mid are Gr1-positive 1A8-negative inflammatory monocytes.

العلاقة: https://figshare.com/articles/journal_contribution/Additional_file_1_of_Inflammatory_monocytes_and_microglia_play_independent_roles_in_inflammatory_ictogenesis/19092429Test

الإتاحة: https://doi.org/10.6084/m9.figshare.19092429.v1Test

المؤلفون: Jintao Xu, Anutosh Ganguly, Jessica Zhao, Michel Ivey, Rafael Lopez, John J. Osterholzer, Clifford S. Cho, Michal A. Olszewski

المصدر: mBio, Vol 12, Iss 4 (2021)

مصطلحات موضوعية: CCR2, cryptococcal meningoencephalitis, central nervous system infections, immunopathogenesis, inflammatory monocyte, Microbiology, QR1-502

الوصف: ABSTRACT Cryptococcal meningoencephalitis (CM) is a leading cause of central nervous system (CNS) infection-related mortality worldwide, with surviving patients often developing neurological deficiencies. While CNS inflammation has been implicated in the pathogenesis of CM, little is known about the relative contribution of the specific inflammatory/immune pathways to CNS pathology versus fungal clearance. Increased cerebrospinal fluid level of C-C chemokine receptor 2 (CCR2) ligand CCL2 is associated with disease deterioration in patients with CM. Using a murine model, we investigated the role of the CCR2 pathway in the development of CNS inflammation and pathology during CM. We found that CCR2-deficient mice exhibited improved 28-day survival and alleviated neurological disease scores despite a brain fungal burden higher than that of the WT mice. Reduced CM pathology in CCR2-deficient mice was accompanied by markedly decreased neuronal cell death around cryptococcal microcysts and restored expression of genes involved in neurotransmission, connectivity, and neuronal cell structure in the brains. Results show that CCR2 axis is the major pathway recruiting CD45hiCD11b+Ly6C+ inflammatory monocyte to the brain and indirectly modulates the accumulation of CD4+ T cells and CD8+ T cells. In particular, CCR2 axis promotes recruitment of interferon gamma (IFN-γ)-producing CD4+ T cells and classical activation of myeloid cells. In this context, CCR2 deletion limits the immune network dysregulation we see in CM and attenuates neuropathology. Thus, the CCR2 axis is a potential target for interventions aimed to limit inflammatory CNS pathology in CM patients. IMPORTANCE Cryptococcal meningoencephalitis (CM) causes nearly 200,000 deaths worldwide each year, and survivors frequently develop long-lasting neurological sequelae. The high rate of mortality and neurologic sequelae in CM patients indicate that antifungal therapies alone are often insufficient to control disease progression. Here, we reveal that CM disease progression in mice is accompanied by inflammatory monocytes infiltration at the periphery of the infected foci that overlap locally perturbed neuronal function and death. Importantly, we identified that CCR2 signaling is a critical pathway driving neuroinflammation, especially inflammatory monocyte recruitment, as well as CNS pathology and mortality in CM mice. Our results imply that targeting the CCR2 pathway may be beneficial as a therapy complementary to antifungal drug treatment, helping to reduce CNS damage and mortality in CM patients.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2150-7511Test

الوصول الحر: https://doaj.org/article/fa96c601b6884e13a47ad60d90871573Test

المؤلفون: Fumi Miyagawa, Yutaka Tagaya, Keiko Ozato, Kyoji Horie, Hideo Asada

المصدر: Journal of Translational Autoimmunity, Vol 3, Iss , Pp 100060- (2020)

مصطلحات موضوعية: SLE, Inflammatory monocyte, Monocyte-derived DC, IRF7, IRF8, Immunologic diseases. Allergy, RC581-607

الوصف: Using a mouse model of systemic lupus erythematosus (SLE), we recently demonstrated that the two major manifestations of SLE are mechanistically independent because the type I IFN pathway leads to the autoantibody production whereas the NF-κB activation is sufficient for the development of glomerulonephritis. To further advance our understandings on the molecular pathways regulating the development of SLE, we studied the role of IRF8 because it controls both type I IFN and NF-κB pathways and saw that IRF8-deficient mice failed to develop either glomerulonephritis or the autoantibody production. Furthermore, these genetically engineered mice prompted us to realize the important role of Ly6Chigh inflammatory monocytes in the development of SLE. These monocytes migrate to the peritoneal cavity in WT and IRF7-deficient mice but not in IRF8-deficient mice, and there they produce both type I IFN and proinflammatory cytokines in WT mice, while in IRF7-deficient mice they only produce proinflammatory cytokines. Upon migration to the spleen, Ly6Chigh inflammatory monocytes differentiate into dendritic cells (DCs) which are capable of producing proinflammatory cytokines in response to dsDNA autoantigen. Collectively, type I IFN produced from inflammatory monocytes/monocyte-derived DCs might be essential for autoantibody production whereas proinflammatory cytokines produced from them might mediate tissue damages in this model. Our study reveals a specialized role for monocyte-derived antigen presenting cells in autoimmunity. Plasticity of monocyte might play an important role not only in the pathogenesis of the disease but also in flare-ups of the disease.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2589909020300277Test; https://doaj.org/toc/2589-9090Test

الوصول الحر: https://doaj.org/article/5abd63627bfd4c84821c0224d850fc51Test

المؤلفون: Ferrari L., Martelli P., Saleri R., De Angelis E., Ferrarini G., Cavalli V., Passeri B., Bazzoli G., Ogno G., Magliani W., Borghetti P.

المساهمون: Ferrari, L., Martelli, P., Saleri, R., De Angelis, E., Ferrarini, G., Cavalli, V., Passeri, B., Bazzoli, G., Ogno, G., Magliani, W., Borghetti, P.

مصطلحات موضوعية: Cytokine, Double positive cytotoxic T lymphocytes (DP CTL), IFN-γ secreting cell, Killer peptide (KP), Natural killer (NK) T cell, Porcine circovirus type 2 (PCV2), Porcine reproductive and respiratory syndrome virus (PRRSV), Pro-inflammatory monocyte, TNF-α, Viral cross-reactivity

الوصف: This study evaluated the early modulation of the phenotype and cytokine secretion in swine immune cells treated with an engineered killer peptide (KP) based on an anti-idiotypic antibody functionally mimicking a yeast killer toxin. The influence of KP on specific immunity was investigated using porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) as ex vivo antigens. Peripheral blood mononuclear cells (PBMC) from healthy pigs were stimulated with KP and with a scramble peptide for 20 min, 1, 4 and 20 h or kept unstimulated. The cells were analyzed using flow cytometry and ELISA. The same time-periods were used for KP pre-incubation/co-incubation to determine the effect on virus-recalled interferon-gamma (IFN-γ) secreting cell (SC) frequencies and single cell IFN-γ productivity using ELISPOT. KP induced an early dose-dependent shift to pro-inflammatory CD172α+CD14+high monocytes and an increase of CD3+CD16+ natural killer (NK) T cells. KP triggered CD8α and CD8β expression on classical CD4−CD8αβ+ cytotoxic T lymphocytes (CTL) and double positive (DP) CD4+CD8α+ Th memory cells (CD4+CD8α+low CD8β+low). A fraction of DP cells also expressed high levels of CD8α. The two identified DP CD4+CD8α+high CD8β+low/+high CTL subsets were associated with tumor necrosis factor alpha (TNF-α) and IFN-γ secretion. KP markedly boosted the reactivity and cross-reactivity of PRRSV type-1- and PCV2b-specific IFN-γ SC. The results indicate the efficacy of KP in stimulating Th1-biased immunomodulation and support studies of KP as an immunomodulator or vaccine adjuvant.

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000572830100012; volume:72; firstpage:1; lastpage:15; numberofpages:15; journal:COMPARATIVE IMMUNOLOGY, MICROBIOLOGY AND INFECTIOUS DISEASES; http://hdl.handle.net/11381/2900169Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85089002527

الإتاحة: https://doi.org/10.1016/j.cimid.2020.101523Test
http://hdl.handle.net/11381/2900169Test