Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple rol...Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.展开更多
BACKGROUND Depression is a significant psychiatric disorder with particularly high prevalence among adolescents.This mental health condition can have severe consequences,including academic failure,social withdrawal,an...BACKGROUND Depression is a significant psychiatric disorder with particularly high prevalence among adolescents.This mental health condition can have severe consequences,including academic failure,social withdrawal,and suicidal behavior.Given the increasing rate of depression in this age group,understanding the underlying biological mechanisms is essential for early detection and intervention.Recent studies have suggested that immune markers play a role in the pathophysiology of depression,prompting further investigation of their potential association with depressive symptoms in adolescents.AIM To investigate the relationship between immune markers(monocytes,lymphocytes,and direct bilirubin)and the incidence and severity of depression among adolescents.METHODS This cross-sectional study recruited 145 adolescent patients with depression[male(M)/female(F)=38/107]from Jiangbin Hospital in Guangxi,Zhuang and 163 healthy controls(M/F=77/86)from routine health check-ups.Blood samples were collected after an overnight fast.Depression severity was measured using the Zung Self-Rating Depression Scale.The inclusion criteria were age 12-24 years,diagnosis of depressive disorder(ICD-10),and no recent antidepressant use.The exclusion criteria included psychiatric comorbidities and serious somatic diseases.Key statistical methods included group comparisons and correlation analyses.RESULTS There was a higher prevalence of females in the depression group(P<0.001).Significant age differences were observed between the groups(Z=9.43,P<0.001).The depression group had higher monocyte(Z=3.43,P<0.001)and lymphocyte(t=2.29,P<0.05)counts,and higher serum direct bilirubin levels(Z=4.72,P<0.001).Monocyte count varied significantly according to depression severity,with lower counts in the mild group(Z=-2.90,P<0.05).A negative correlation between age and lymphocyte counts was observed(ρ=-0.22,P<0.01).Logistic regression analysis showed that serum direct bilirubin levels significantly predicted depression.CONCLUSION The potential role of elevated levels of immune markers in the early detection of depression in adolescents has been highlighted.Therefore,it is necessary to explore further the relationships between these immune markers and depression.展开更多
Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underp...Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underpinnings of polytrauma-induced immune dysregulation require further investigation.While previous studies examined either injury site tissue or systemic tissue(peripheral blood),our study uniquely investigated both systemic and local immune cells at the same time to better understand polytrauma-induced immune dysregulation and associated impaired bone healing.Using single-cell RNA sequencing(scRNA-seq)in a rat polytrauma model,we analyzed blood,bone marrow,and the local defect soft tissue to identify potential cellular and molecular targets involved in immune dysregulation.We identified a trauma-associated immunosuppressive myeloid(TIM)cell population that drives systemic immune dysregulation,immunosuppression,and potentially impaired bone healing.We found CD1d as a global marker for TIM cells in polytrauma.展开更多
BACKGROUND Deficient efferocytosis(i.e.,phagocytic clearance of apoptotic cells)by macrophages has been frequently reported in experimental models of type 2 diabetes(T2D).AIM To translate these findings to humans by t...BACKGROUND Deficient efferocytosis(i.e.,phagocytic clearance of apoptotic cells)by macrophages has been frequently reported in experimental models of type 2 diabetes(T2D).AIM To translate these findings to humans by testing whether the efferocytosis capacity of blood monocytes and monocyte-derived macrophages is impaired in T2D patients.METHODS Overall,30 patients with poorly controlled T2D[glycosylated hemoglobin(HbA1c)≥8.0%]and 30 age-and sex-matched control subjects were enrolled in the study.The efferocytosis capacities of peripheral blood monocytes and monocyte-derived macrophages were assessed by flow cytometry and immunostaining.Macrophage membrane CD14 expression was examined by flow cytometry.Metabolic factors such as 25(OH)D and immune factors such as interleukin-1βwere also measured.RESULTS The mean monocyte efferocytosis index in the diabetes group was significantly lower than that in the control group.Notably,efferocytosis remained impaired after monocytes differentiated into macrophages.Additionally,the percentages of classical monocytes(CD14^(++)CD16-monocytes)and CD14^(+)macrophages were significantly lower in the diabetes group.Multivariate linear regression analysis in diabetes patients demonstrated that the monocyte efferocytosis index was independently associated with the HbA1c level,and that the macrophage efferocytosis index was significantly associated with the percentage of CD14^(+)macrophages.CONCLUSION Impaired efferocytosis was observed in T2D patients,with poor glycemic control affecting both blood monocytes and monocyte-derived macrophages.The efferocytosis index was negatively associated with metrics of glycemic control,and glucotoxicity may impact efferocytosis through reducing CD14 expression on both monocytes and macrophages.展开更多
AIM： To generate dendritic cells （DCs） from human peripheral blood and to detect the expression of dendritic cell-specific intercellular adhesion molecule 3 grabbing nonintegrin （DC-SIGN; CD209） for the further s...AIM： To generate dendritic cells （DCs） from human peripheral blood and to detect the expression of dendritic cell-specific intercellular adhesion molecule 3 grabbing nonintegrin （DC-SIGN; CD209） for the further study of DC-SIGN in hepatitis C virus （HCV） transmission. METHODS： Peripheral blood monocytes were isolated from blood of healthy individuals by Ficoll--Hypaque sedimentation and cultured in complete medium containing rhGM-CSF and rhIL-4. Cells were cultured for seven days, with cytokine addition every two days to obtain immature DCs. Characteristics of the cultured cells were observed under light and scanning microscope, and the expression of DC-SIGN was detected by immunofluorescence staining. RESULTS： After seven-day culture, a large number of cells with typical characteristics of DCs appeared. Their characteristics were observed under light and scanning electron microscope. These cells had a variety of cell shapes such as those of bipolar elongate cells, elaborate stellate cells and DCs. DC-SIGN was detected by immunofluorescence staining and its expression level on cultivated dendritic cells was high. CONCLUSION： DCs with a high expression of DC-SIGN can be generated from human peripheral blood monocytes in complete medium containing rhGM-CSF and rhIL-4.展开更多
Aim This study was to evaluate the effect of arsenic trioxide （As2O3） on the transgenic TNF-α promoter activity in cultured vascular smooth muscle cells （VSMCs） and THP-1 monocytes. Methods Human TNF-α promoter ...Aim This study was to evaluate the effect of arsenic trioxide （As2O3） on the transgenic TNF-α promoter activity in cultured vascular smooth muscle cells （VSMCs） and THP-1 monocytes. Methods Human TNF-α promoter was constructed by reporter gene system and was transiently transfected into VSMCs and THP-1 in vitro. The promoter activity was tested by luciferase activity with or without LPS and Ang Ⅱ stimulation, before and after different dosage of As2O3 treatment. Results 1. TNF-α promoter effectively expressed in VSMCs and THP-1 compared with CMV promoter （58.3% and 80.9%, respectively）. Both LPS and Ang Ⅱ significantly up-regulated TNF-α promoter activity （P〈0.05）. 2. As2O3 significantly inhibited, both intact and LPS/Ang Ⅱ stimulated promoter activity, in a dose dependent manner （P〈0.05）, and in both cell type. Conclusion These results manifested that, the inhibition effect of As2O3 on the activity of human TNF-α promoter indicated its potential inhibition on pro-inflammatory cytokine genes expression at transcriptional level and its potential anti-inflammatory property in the cardiovascular system.展开更多
Objective: In order to detect the role of monocytes inHSV-2 infection, we studied the effect of herpes sim-plex Virus-2 infection on the production of tumor ne-crosis factor (TNF-σ), interleukin-6 (IL-6) secretedby m...Objective: In order to detect the role of monocytes inHSV-2 infection, we studied the effect of herpes sim-plex Virus-2 infection on the production of tumor ne-crosis factor (TNF-σ), interleukin-6 (IL-6) secretedby monocytes. Methods: Monocytes were infected by HSV-2 (333Strain). Culture supernatants were collected at 1, 3,5, 7 days post-infection. The levels of TNF-α, IL-6were measured by enzyme-linked immunosorbent as-say (ELISA). Results: The levels of TNF-α secretion by mono-cytes significantly decreased on first day post-infection. The levels of IL-6 significantly decreasedon first and third days post-infection, and then gradu-ally increased to the control on seventh day post-infection. Conclusions: TNF-α and IL-6 production by mono-cytes was inhibited during HSV-2 infection. The pro-duction of cytokines may play an important role inherpes simplex viurs-2 pathogenicity and immunity.展开更多
Objectives: In order to investigate the role of mono-cytes and human leukocyte antigen (HLA) class II an-tigen in herpes simplex virus-2 (HSV-2) infection, westudied the effect of HSV-2 infection in vitro on theexpres...Objectives: In order to investigate the role of mono-cytes and human leukocyte antigen (HLA) class II an-tigen in herpes simplex virus-2 (HSV-2) infection, westudied the effect of HSV-2 infection in vitro on theexpression of HLA class II antigen on monocytes.Methods: Monocytes were infected with HSV-2(Strain 333). Culture cells were collected 1, 3, 5 and 7days after infection. The levels of expression of HLAclass II antigen were measured by using alkaline phos-phatase antialkaline phosphatase method (APAAP).Results: The levels of the expression of HLA class IIantigen on monocytes significantly decreased on thefirst day of post-infection, and then gradually returnedto levels found in the controls by the 7th day post-infection.Conclusion: HLA class II antigen expression onmonocytes was inhibited with HSV-2 infection, whichmight be one means of virus escape at an early phase.The expression of HLA class II antigen may play animportant role in herpes simplex viurs-2 pathogenic-ity and immunity.展开更多
Monocytes play a crucial role in post-stroke immune infiltration,yet the intricate immune regulatory networks they orchestrate in ischemic stroke remain poorly understood.This knowledge gap has hindered the developmen...Monocytes play a crucial role in post-stroke immune infiltration,yet the intricate immune regulatory networks they orchestrate in ischemic stroke remain poorly understood.This knowledge gap has hindered the development of targeted monocyte-based therapies for stroke.Here,we used a multi-omics approach combining single-cell and bulk transcriptomics.CellChat analysis revealed intercellular communication networks,while key genes were identified and predictive models built through Lasso regression.Immune cell infiltration dynamics were quantified using single-sample gene set enrichment analysis.Gene set enrichment analysis and gene set variation analysis identified disease-regulated pathways of core genes.MicroRNA networks and transcription factors were investigated using mircode and RcisTarget.Experimental validation was performed using oxygen-glucose deprivation and transient middle cerebral artery occlusion models,focusing on the influence of abhydrolase domain-containing protein 2 on monocyte function.We observed significantly elevated monocyte content in stroke brain tissue samples,and identified key monocyte genes associated with immune inflammation,chemokine signaling,and cell receptor function.A robust seven-gene predictive model for ischemic stroke was developed.CD274 strongly correlated with these seven genes,suggesting a potential immunomodulatory axis.In vivo transient middle cerebral artery occlusion experiments validated the predictive value of key genes.In vitro studies demonstrated that abhydrolase domain-containing protein 2 overexpression enhanced monocyte proliferation and phagocytic activity post-oxygen-glucose deprivation while reducing reactive oxygen species generation.In conclusion,this study maps post-stroke monocyte communication networks,identifies key signaling pathways,identifies regulatory mechanisms,and validates the functional importance of key genes,particularly abhydrolase domain-containing protein 2.These findings provide a foundation for developing targeted immunomodulatory therapies and precision diagnostics in ischemic stroke management.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82060219,82271234the Natural Science Foundation of Jiangxi Province,Nos.20212ACB216009,20212BAB216048+1 种基金Jiangxi Province Thousands of Plans,No.jxsq2019201023Youth Team Project of the Second Affiliated Hospital of Nanchang University,No.2019YNTD12003(all to FH)。
文摘Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.
基金Supported by the Medical Discipline Construction Project of Pudong Health Committee of Shanghai,No.PWZzb2022-09Nanning City Science Research and Technology Development Program,No.ZC20233017and Guangxi Medical and Health Appropriate Technology Development and Promotion Project,No.S2021061.
文摘BACKGROUND Depression is a significant psychiatric disorder with particularly high prevalence among adolescents.This mental health condition can have severe consequences,including academic failure,social withdrawal,and suicidal behavior.Given the increasing rate of depression in this age group,understanding the underlying biological mechanisms is essential for early detection and intervention.Recent studies have suggested that immune markers play a role in the pathophysiology of depression,prompting further investigation of their potential association with depressive symptoms in adolescents.AIM To investigate the relationship between immune markers(monocytes,lymphocytes,and direct bilirubin)and the incidence and severity of depression among adolescents.METHODS This cross-sectional study recruited 145 adolescent patients with depression[male(M)/female(F)=38/107]from Jiangbin Hospital in Guangxi,Zhuang and 163 healthy controls(M/F=77/86)from routine health check-ups.Blood samples were collected after an overnight fast.Depression severity was measured using the Zung Self-Rating Depression Scale.The inclusion criteria were age 12-24 years,diagnosis of depressive disorder(ICD-10),and no recent antidepressant use.The exclusion criteria included psychiatric comorbidities and serious somatic diseases.Key statistical methods included group comparisons and correlation analyses.RESULTS There was a higher prevalence of females in the depression group(P<0.001).Significant age differences were observed between the groups(Z=9.43,P<0.001).The depression group had higher monocyte(Z=3.43,P<0.001)and lymphocyte(t=2.29,P<0.05)counts,and higher serum direct bilirubin levels(Z=4.72,P<0.001).Monocyte count varied significantly according to depression severity,with lower counts in the mild group(Z=-2.90,P<0.05).A negative correlation between age and lymphocyte counts was observed(ρ=-0.22,P<0.01).Logistic regression analysis showed that serum direct bilirubin levels significantly predicted depression.CONCLUSION The potential role of elevated levels of immune markers in the early detection of depression in adolescents has been highlighted.Therefore,it is necessary to explore further the relationships between these immune markers and depression.
文摘Polytrauma with significant bone and volumetric muscle loss presents substantial clinical challenges.Although immune responses significantly influence fracture healing post-polytrauma,the cellular and molecular underpinnings of polytrauma-induced immune dysregulation require further investigation.While previous studies examined either injury site tissue or systemic tissue(peripheral blood),our study uniquely investigated both systemic and local immune cells at the same time to better understand polytrauma-induced immune dysregulation and associated impaired bone healing.Using single-cell RNA sequencing(scRNA-seq)in a rat polytrauma model,we analyzed blood,bone marrow,and the local defect soft tissue to identify potential cellular and molecular targets involved in immune dysregulation.We identified a trauma-associated immunosuppressive myeloid(TIM)cell population that drives systemic immune dysregulation,immunosuppression,and potentially impaired bone healing.We found CD1d as a global marker for TIM cells in polytrauma.
基金Supported by National Natural Science Foundation of China,No.81970669,No.82170835,and No.82100848Shanghai Municipal Health Commission,No.202240107,and No.20234Y0040China Endocrine Metabolism Research Program of Excellence,No.2023-N-03-05。
文摘BACKGROUND Deficient efferocytosis(i.e.,phagocytic clearance of apoptotic cells)by macrophages has been frequently reported in experimental models of type 2 diabetes(T2D).AIM To translate these findings to humans by testing whether the efferocytosis capacity of blood monocytes and monocyte-derived macrophages is impaired in T2D patients.METHODS Overall,30 patients with poorly controlled T2D[glycosylated hemoglobin(HbA1c)≥8.0%]and 30 age-and sex-matched control subjects were enrolled in the study.The efferocytosis capacities of peripheral blood monocytes and monocyte-derived macrophages were assessed by flow cytometry and immunostaining.Macrophage membrane CD14 expression was examined by flow cytometry.Metabolic factors such as 25(OH)D and immune factors such as interleukin-1βwere also measured.RESULTS The mean monocyte efferocytosis index in the diabetes group was significantly lower than that in the control group.Notably,efferocytosis remained impaired after monocytes differentiated into macrophages.Additionally,the percentages of classical monocytes(CD14^(++)CD16-monocytes)and CD14^(+)macrophages were significantly lower in the diabetes group.Multivariate linear regression analysis in diabetes patients demonstrated that the monocyte efferocytosis index was independently associated with the HbA1c level,and that the macrophage efferocytosis index was significantly associated with the percentage of CD14^(+)macrophages.CONCLUSION Impaired efferocytosis was observed in T2D patients,with poor glycemic control affecting both blood monocytes and monocyte-derived macrophages.The efferocytosis index was negatively associated with metrics of glycemic control,and glucotoxicity may impact efferocytosis through reducing CD14 expression on both monocytes and macrophages.
文摘目的:探讨单核细胞/淋巴细胞比值(monocyte to lymphocyte ratio,MLR)、全身免疫炎症指数(systemic immune inflammation index,SII)与口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)患者临床病理特征及预后的相关性。方法:选取口腔鳞状细胞癌患者93例作为观察组,以同期体检正常的志愿者86例作为对照组。比较两组MLR、SII水平;比较不同病理分级、病理分期、有无淋巴结转移患者MLR、SII水平。93例OSCC患者术后随访期间复发或死亡37例为预后不良组,其余56例为预后良好组,比较两组MLR、SII水平。绘制受试者工作特征(receiver operating characteristic,ROC)曲线,并计算曲线下面积(area under curve,AUC),分析MLR、SII单独及联合检测对OSCC患者预后不良的预测价值。结果:观察组血液MLR、SII水平为0.690±0.174、(512.4±122.3)×10~9/L,分别高于对照组的0.509±0.136和(385.5±109.1)×10~9/L(均P<0.001)。中低分化患者MLR(0.729±0.168 vs 0.635±0.170)、SII[(540.2±119.4)×10~9/L vs(472.2±116.5)×10~9/L]水平高于高分化患者;临床分期Ⅲ~Ⅳ期患者MLR(0.789±0.140 vs 0.636±0.168)、SII[(588.0±108.7)×10~9/L vs(470.9±109.4)×10~9/L]水平高于临床分期Ⅰ~Ⅱ期患者;淋巴结转移的口腔癌患者MLR(0.754±0.163 vs 0.659±0.171)、SII[(561.3±115.9)×10~9/L vs(485.6±118.2)×10~9/L]水平高于无淋巴结转移患者(均P<0.01)。预后不良组MLR、SII水平为0.731±0.173、(542.1±125.3)×10~9/L,分别高于预后良好组的0.663±0.171、(491.9±117.0)×10~9/L(均P<0.001)。ROC曲线分析显示,MLR、SII单独预测OSCC患者预后不良的AUC分别为0.765、0.751,低于MLR、SII联合预测的AUC 0.783(均P<0.001)。结论:口腔鳞状细胞癌患者MLR、SII水平异常升高,与肿瘤恶性程度及不良预后密切相关,MLR与SII联合检测可显著提升OSCC患者预后评估的准确性。
基金Supported by the National Natural Science Foundation of China,No.30170822
文摘AIM： To generate dendritic cells （DCs） from human peripheral blood and to detect the expression of dendritic cell-specific intercellular adhesion molecule 3 grabbing nonintegrin （DC-SIGN; CD209） for the further study of DC-SIGN in hepatitis C virus （HCV） transmission. METHODS： Peripheral blood monocytes were isolated from blood of healthy individuals by Ficoll--Hypaque sedimentation and cultured in complete medium containing rhGM-CSF and rhIL-4. Cells were cultured for seven days, with cytokine addition every two days to obtain immature DCs. Characteristics of the cultured cells were observed under light and scanning microscope, and the expression of DC-SIGN was detected by immunofluorescence staining. RESULTS： After seven-day culture, a large number of cells with typical characteristics of DCs appeared. Their characteristics were observed under light and scanning electron microscope. These cells had a variety of cell shapes such as those of bipolar elongate cells, elaborate stellate cells and DCs. DC-SIGN was detected by immunofluorescence staining and its expression level on cultivated dendritic cells was high. CONCLUSION： DCs with a high expression of DC-SIGN can be generated from human peripheral blood monocytes in complete medium containing rhGM-CSF and rhIL-4.
基金National Natural Science Foundation of China(No.30170368)
文摘Aim This study was to evaluate the effect of arsenic trioxide （As2O3） on the transgenic TNF-α promoter activity in cultured vascular smooth muscle cells （VSMCs） and THP-1 monocytes. Methods Human TNF-α promoter was constructed by reporter gene system and was transiently transfected into VSMCs and THP-1 in vitro. The promoter activity was tested by luciferase activity with or without LPS and Ang Ⅱ stimulation, before and after different dosage of As2O3 treatment. Results 1. TNF-α promoter effectively expressed in VSMCs and THP-1 compared with CMV promoter （58.3% and 80.9%, respectively）. Both LPS and Ang Ⅱ significantly up-regulated TNF-α promoter activity （P〈0.05）. 2. As2O3 significantly inhibited, both intact and LPS/Ang Ⅱ stimulated promoter activity, in a dose dependent manner （P〈0.05）, and in both cell type. Conclusion These results manifested that, the inhibition effect of As2O3 on the activity of human TNF-α promoter indicated its potential inhibition on pro-inflammatory cytokine genes expression at transcriptional level and its potential anti-inflammatory property in the cardiovascular system.
文摘Objective: In order to detect the role of monocytes inHSV-2 infection, we studied the effect of herpes sim-plex Virus-2 infection on the production of tumor ne-crosis factor (TNF-σ), interleukin-6 (IL-6) secretedby monocytes. Methods: Monocytes were infected by HSV-2 (333Strain). Culture supernatants were collected at 1, 3,5, 7 days post-infection. The levels of TNF-α, IL-6were measured by enzyme-linked immunosorbent as-say (ELISA). Results: The levels of TNF-α secretion by mono-cytes significantly decreased on first day post-infection. The levels of IL-6 significantly decreasedon first and third days post-infection, and then gradu-ally increased to the control on seventh day post-infection. Conclusions: TNF-α and IL-6 production by mono-cytes was inhibited during HSV-2 infection. The pro-duction of cytokines may play an important role inherpes simplex viurs-2 pathogenicity and immunity.
文摘Objectives: In order to investigate the role of mono-cytes and human leukocyte antigen (HLA) class II an-tigen in herpes simplex virus-2 (HSV-2) infection, westudied the effect of HSV-2 infection in vitro on theexpression of HLA class II antigen on monocytes.Methods: Monocytes were infected with HSV-2(Strain 333). Culture cells were collected 1, 3, 5 and 7days after infection. The levels of expression of HLAclass II antigen were measured by using alkaline phos-phatase antialkaline phosphatase method (APAAP).Results: The levels of the expression of HLA class IIantigen on monocytes significantly decreased on thefirst day of post-infection, and then gradually returnedto levels found in the controls by the 7th day post-infection.Conclusion: HLA class II antigen expression onmonocytes was inhibited with HSV-2 infection, whichmight be one means of virus escape at an early phase.The expression of HLA class II antigen may play animportant role in herpes simplex viurs-2 pathogenic-ity and immunity.
基金National Natural Science Foundation of China,No.82471361(to MZ)the Natural Science Foundation for Excellent Young Scholars of Hunan Province,No.2021JJ20095(to MZ)+3 种基金the Key Research and Development Program of Hunan Province,No.2020SK2063(to MZ)the Research Project on Education and Teaching Innovation of Central South University,No.2021jy145(to MZ)the Natural Science Foundations of Hunan Province,No.2020JJ4134(to MZ)the Fundamental Research Funds for the Central Universities of Central South University,No.2023ZZTS0595(to YP).
文摘Monocytes play a crucial role in post-stroke immune infiltration,yet the intricate immune regulatory networks they orchestrate in ischemic stroke remain poorly understood.This knowledge gap has hindered the development of targeted monocyte-based therapies for stroke.Here,we used a multi-omics approach combining single-cell and bulk transcriptomics.CellChat analysis revealed intercellular communication networks,while key genes were identified and predictive models built through Lasso regression.Immune cell infiltration dynamics were quantified using single-sample gene set enrichment analysis.Gene set enrichment analysis and gene set variation analysis identified disease-regulated pathways of core genes.MicroRNA networks and transcription factors were investigated using mircode and RcisTarget.Experimental validation was performed using oxygen-glucose deprivation and transient middle cerebral artery occlusion models,focusing on the influence of abhydrolase domain-containing protein 2 on monocyte function.We observed significantly elevated monocyte content in stroke brain tissue samples,and identified key monocyte genes associated with immune inflammation,chemokine signaling,and cell receptor function.A robust seven-gene predictive model for ischemic stroke was developed.CD274 strongly correlated with these seven genes,suggesting a potential immunomodulatory axis.In vivo transient middle cerebral artery occlusion experiments validated the predictive value of key genes.In vitro studies demonstrated that abhydrolase domain-containing protein 2 overexpression enhanced monocyte proliferation and phagocytic activity post-oxygen-glucose deprivation while reducing reactive oxygen species generation.In conclusion,this study maps post-stroke monocyte communication networks,identifies key signaling pathways,identifies regulatory mechanisms,and validates the functional importance of key genes,particularly abhydrolase domain-containing protein 2.These findings provide a foundation for developing targeted immunomodulatory therapies and precision diagnostics in ischemic stroke management.
