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1.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(4): 373-378, 2021 Apr 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33967083

RESUMO

OBJECTIVES: To investigate the level and significance of serum γ-glutamyl transferase-to-platelet ratio (GPR) and monocyte count to high-density lipoprotein ratio (MHR) in patients with essential hypertension (EH) and unstable angina (UA). METHODS: A total of 218 patients with coronary angiography aged ≥60 years, who were admitted to the EH hospital of the Department of Cardiac Medicine, Affiliated Hospital of Chengde Medical College, were selected from September 2018 to September 2019. They were divided into an EH+UA group (n=113) and an EH group (n=105). In addition, 106 patients with normal coronary angiography who were diagnosed with coronary heart disease were selected as a control group. The general data, blood biochemical indicators, GPR and MHR in each group were compared, and partial correlation analysis and receiver operator characteristic (ROC) curve analysis were performed. RESULTS: Compared with the control group, patients in the EH+UA group and the EH group had higher body mass index (BMI), tyiglyceride (TG), GPR, and MHR, and lower high-density lipoprotein-cholesterol (HDL-C) (all P<0.05); and patients in the EH+UA group had higher white blood cell counts, alanine aminotransferase (ALT), and uric acid (all P<0.05). Compared with the EH group, patients in the EH+UA group had higher GPR and MHR (both P<0.05). Partial correlation analysis showed that after controlling the antihypertensive drugs and lipid-lowering drugs, GPR was found to be positively correlated with BMI, white blood cell count, ALT, TG, and uric acid (r=0.160, 0.111, 0.205, 0.250, 0.154, respectively, all P<0.05), which was negatively correlated with HDL-C (r=-0.238, P<0.05); MHR was positively correlated with BMI, ALT, TG, uric acid, and GPR (r=0.186, 0.307, 0.157, 0.141, 0.223, respectively, all P<0.05), and negatively correlated with HDL-C (r=-0.610, P<0.001). ROC curve analysis showed that GPR had higher specificity and positive predictive value, while MHR had higher sensitivity. When the two indicators were combined, the sensitivity and positive predictive value were higher. CONCLUSIONS: There is a correlation between GPR, MHR and EH combined with UA pectoris, and the combined detection of the two indicators has adjuvant diagnostic value for elderly EH combined with UA.


Assuntos
Angina Instável , Lipoproteínas HDL , Idoso , HDL-Colesterol , Angiografia Coronária , Hipertensão Essencial , Humanos , Monócitos
2.
Croat Med J ; 62(2): 154-164, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33938655

RESUMO

AIM: To assess the correlations of B regulatory cells (Bregs) and monocyte subsets in peripheral blood with the National Institutes of Health (NIH)-consensus-defined clinical manifestations of chronic graft-vs-host disease (cGvHD), in an attempt to establish their role as cellular biomarkers. METHODS: This multidisciplinary prospective study enrolled adult cGVHD patients treated in the University Hospital Center Zagreb and University of Zagreb School of Medicine. Immunophenotypic subpopulations of CD24highCD38high Bregs (CD27-, CD27+, and total) and monocyte (classical, intermediate, and non-classical) counts were correlated with demographic, transplant, and cGVHD-related data. Bivariate correlation analysis was performed to evaluate the correlations between Bregs and monocytes subsets and cGVHD organ involvement, as well as cGVHD severity and immunosuppression intensity. RESULTS: Twenty-two adult patients (54.5% female) with cGVHD were enrolled. The median (range) age was 44.5 years (24-65). All patients were transplanted for hematologic malignancies and 40.9% had severe NIH cGVHD global score. The median time from cGVHD diagnosis to the analysis was 16.6 months (0-176). The organ most frequently affected with cGVHD were the eyes (68.2%), skin (45.5%), lungs (45.5%), and liver (40.9%). Lower total and CD27-Bregs counts were correlated with worse cGVHD severity, higher immunosuppression intensity, and lung cGVHD, in terms of cell count, but also with skin cGVHD, in terms of percentages. Patients with liver and joint/fascia cGVHD had a lower percentage of non-classical monocytes and patients with more severe global NIH score had a higher classical monocytes count. CONCLUSION: Different organs affected by cGVHD are differently associated with different subpopulations of Bregs and monocytes.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Idoso , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos , Estudos Prospectivos , Estados Unidos , Adulto Jovem
3.
J Zoo Wildl Med ; 52(1): 348-356, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33827198

RESUMO

Ecophysiology and conservation studies often require the prior establishment of baseline physiologic metrics. For instance, expected reference intervals for health metrics are valuable tools for veterinarians and conservationists who monitor the health status of endangered populations and species. This study establishes reference intervals for hematologic metrics in free-ranging Olrog's gull (Larus atlanticus) during the nonbreeding season. Fifty-six gulls (immature and adults) were captured and studied in Mar del Plata and neighboring coastal areas (Buenos Aires, Argentina) during the winter of 2018 (n = 22) and 2019 (n = 34). Hematocrit, red blood cells (erythrocytes), hemoglobin, mean cell volume, mean cell hemoglobin (MCH), MCH concentration, white blood cells (WBC; leukocytes), heterophils, lymphocytes, eosinophils, monocytes, and basophils were analyzed. Additionally, the variability of hematologic metrics according to body weight, sex, age, and calendar year was examined. Hematologic metrics were in line with those reported in other seabird species. Males had greater body weight and MCH than females. The heterophil to lymphocyte ratio and lymphocyte levels were higher in adults than in immatures. Hematocrit, WBC, heterophils, and basophils also varied significantly between calendar years. The results highlight the importance of appropriate metrics and reference intervals for monitoring the health status of this threatened species, and it is recommended to implement such comparative assessments among populations.


Assuntos
Charadriiformes/sangue , Estações do Ano , Envelhecimento , Animais , Argentina , Ascomicetos , Basófilos , Eosinófilos , Contagem de Eritrócitos , Índices de Eritrócitos , Feminino , Hematócrito , Hemoglobinas , Contagem de Leucócitos , Linfócitos , Masculino , Monócitos
4.
Front Immunol ; 12: 645124, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33897692

RESUMO

Background: The major histocompatibility complex (MHC) class II characterized by monocytes CD14+ expression of human leukocyte antigen receptors (HLA-DR), is essential for the synapse between innate and adaptive immune response in infectious disease. Its reduced expression is associated with a high risk of secondary infections in septic patients and can be safely corrected by Interferon-y (IFNy) injection. Coronavirus disease (COVID-19) induces an alteration of Interferon (IFN) genes expression potentially responsible for the observed low HLA-DR expression in circulating monocytes (mHLA-DR). Methods: We report a case of one-time INFy injection (100 mcg s.c.) in a superinfected 61-year-old man with COVID-19-associated acute respiratory distress syndrome (ARDS), with monitoring of mHLA-DR expression and clinical tolerance. Observations: Low mHLA-DR pretreatment expression (26.7%) was observed. IFNy therapy leading to a rapid increase in mHLA-DR expression (83.1%). Conclusions: Severe ARDS in a COVID-19 patient has a deep reduction in mHLA-DR expression concomitantly with secondary infections. The unique IFNy injection was safe and led to a sharp increase in the expression of mHLA-DR. Based on immune and infection monitoring, more cases of severe COVID-19 patients with low mHLA-DR should be treated by IFNy to test the clinical effectiveness.


Assuntos
Síndrome de Imunodeficiência Adquirida , Antígenos HLA-DR/imunologia , Interferon gama/administração & dosagem , Monócitos/imunologia , Índice de Gravidade de Doença , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/imunologia , Síndrome de Imunodeficiência Adquirida/patologia , /imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/patologia
5.
Int J Mol Sci ; 22(5)2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800150

RESUMO

Celiac disease (CD) is a frequent intestinal inflammatory disease occurring in genetically susceptible individuals upon gluten ingestion. Recent studies point to a role in CD for genes involved in cell shape, adhesion and actin rearrangements, including a Rho family regulator, Rho GTPase-activating protein 31 (ARHGAP31). In this study, we investigated the morphology and actin cytoskeletons of peripheral monocyte-derived dendritic cells (DCs) from children with CD and controls when in contact with a physiological substrate, fibronectin. DCs were generated from peripheral blood monocytes of pediatric CD patients and controls. After adhesion on fibronectin, DCs showed a higher number of protrusions and a more elongated shape in CD patients compared with controls, as assessed by immunofluorescence actin staining, transmitted light staining and video time-lapse microscopy. These alterations did not depend on active intestinal inflammation associated with gluten consumption and were specific to CD, since they were not found in subjects affected by other intestinal inflammatory conditions. The elongated morphology was not a result of differences in DC activation or maturation status, and did not depend on the human leukocyte antigen (HLA)-DQ2 haplotype. Notably, we found that ARH-GAP31 mRNA levels were decreased while RhoA-GTP activity was increased in CD DCs, pointing to an impairment of the Rho pathway in CD cells. Accordingly, Rho inhibition was able to prevent the cytoskeleton rearrangements leading to the elongated morphology of celiac DCs upon adhesion on fibronectin, confirming the role of this pathway in the observed phenotype. In conclusion, adhesion on fibronectin discriminated CD from the controls' DCs, revealing a gluten-independent CD-specific cellular phenotype related to DC shape and regulated by RhoA activity.


Assuntos
Actinas/metabolismo , Doença Celíaca/metabolismo , Forma Celular , Células Dendríticas/imunologia , Monócitos/metabolismo , Doença Celíaca/patologia , Adesão Celular , Criança , Pré-Escolar , Células Dendríticas/patologia , Feminino , Fibronectinas/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Antígenos HLA-DQ/metabolismo , Humanos , Masculino , Monócitos/patologia , Fosfoproteínas/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
6.
Int J Mol Sci ; 22(5)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802280

RESUMO

Monocyte to macrophage differentiation is characterized by the activation of various signal transduction pathways, which may be modulated by protein phosphorylation; however, the impact of protein kinases and phosphatases is not well understood yet. It has been demonstrated that actomyosin rearrangement during macrophage differentiation is dependent on Rho-associated protein kinase (ROCK). Myosin phosphatase (MP) target subunit-1 (MYPT1) is one of the major cellular substrates of ROCK, and MP is often a counter enzyme of ROCK; therefore, MP may also control macrophage differentiation. Changes in MP activity and the effects of MP activation were studied on PMA or l,25(OH)2D3-induced differentiation of monocytic THP-1 cells. During macrophage differentiation, phosphorylation of MYPT1 at Thr696 and Thr853 increased significantly, resulting in inhibition of MP. The ROCK inhibitor H1152 and the MP activator epigallocatechin-3-gallate (EGCG) attenuated MYPT1 phosphorylation and concomitantly decreased the extent of phosphorylation of 20 kDa myosin light chain. H1152 and EGCG pretreatment also suppressed the expression of CD11b and weakened the PMA-induced adherence of the cells. Our results indicate that MP activation/inhibition contributes to the efficacy of monocyte to macrophage differentiation, and this enzyme may be a target for pharmacological interventions in the control of disease states that are affected by excessive macrophage differentiation.


Assuntos
Diferenciação Celular/fisiologia , Macrófagos/metabolismo , Monócitos/metabolismo , Fosfatase de Miosina-de-Cadeia-Leve/metabolismo , Células THP-1/metabolismo , Células Cultivadas , Humanos , Macrófagos/fisiologia , Monócitos/fisiologia , Fosforilação/fisiologia , Transdução de Sinais/fisiologia , Células THP-1/fisiologia , Quinases Associadas a rho/metabolismo
7.
Int J Mol Sci ; 22(5)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802410

RESUMO

Cystic fibrosis (CF) lung disease is dominated by the recruitment of myeloid cells (neutrophils and monocytes) from the blood which fail to clear the lung of colonizing microbes. In prior in vitro studies, we showed that blood neutrophils migrated through the well-differentiated lung epithelium into the CF airway fluid supernatant (ASN) mimic the dysfunction of CF airway neutrophils in vivo, including decreased bactericidal activity despite an increased metabolism. Here, we hypothesized that, in a similar manner to neutrophils, blood monocytes undergo significant adaptations upon recruitment to CFASN. To test this hypothesis, primary human blood monocytes were transmigrated in our in vitro model into the ASN from healthy control (HC) or CF subjects to mimic in vivo recruitment to normal or CF airways, respectively. Surface phenotype, metabolic and bacterial killing activities, and transcriptomic profile by RNA sequencing were quantified post-transmigration. Unlike neutrophils, monocytes were not metabolically activated, nor did they show broad differences in activation and scavenger receptor expression upon recruitment to the CFASN compared to HCASN. However, monocytes recruited to CFASN showed decreased bactericidal activity. RNASeq analysis showed strong effects of transmigration on monocyte RNA profile, with differences between CFASN and HCASN conditions, notably in immune signaling, including lower expression in the former of the antimicrobial factor ISG15, defensin-like chemokine CXCL11, and nitric oxide-producing enzyme NOS3. While monocytes undergo qualitatively different adaptations from those seen in neutrophils upon recruitment to the CF airway microenvironment, their bactericidal activity is also dysregulated, which could explain why they also fail to protect CF airways from infection.


Assuntos
Adaptação Fisiológica/genética , Microambiente Celular/genética , Fibrose Cística/genética , Pulmão/patologia , Monócitos/patologia , Transcrição Genética/genética , Adulto , Células Cultivadas , Feminino , Humanos , Masculino , Neutrófilos/patologia , Transdução de Sinais/fisiologia
8.
Nat Commun ; 12(1): 2027, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795674

RESUMO

The immune response to mycobacteria is characterized by granuloma formation, which features multinucleated giant cells as a unique macrophage type. We previously found that multinucleated giant cells result from Toll-like receptor-induced DNA damage and cell autonomous cell cycle modifications. However, the giant cell progenitor identity remained unclear. Here, we show that the giant cell-forming potential is a particular trait of monocyte progenitors. Common monocyte progenitors potently produce cytokines in response to mycobacteria and their immune-active molecules. In addition, common monocyte progenitors accumulate cholesterol and lipids, which are prerequisites for giant cell transformation. Inducible monocyte progenitors are so far undescribed circulating common monocyte progenitor descendants with high giant cell-forming potential. Monocyte progenitors are induced in mycobacterial infections and localize to granulomas. Accordingly, they exhibit important immunological functions in mycobacterial infections. Moreover, their signature trait of high cholesterol metabolism may be piggy-backed by mycobacteria to create a permissive niche.


Assuntos
Citocinas/imunologia , Células Gigantes/imunologia , Macrófagos/imunologia , Monócitos/imunologia , Células-Tronco/imunologia , Animais , Células Cultivadas , Citocinas/metabolismo , Feminino , Células Gigantes/metabolismo , Células Gigantes/microbiologia , Granuloma/imunologia , Granuloma/metabolismo , Humanos , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Monócitos/metabolismo , Monócitos/microbiologia , Mycobacterium/imunologia , Mycobacterium/fisiologia , Células-Tronco/metabolismo , Células-Tronco/microbiologia
9.
Front Immunol ; 12: 649567, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33841434

RESUMO

Both coronavirus disease 2019 (COVID-19) and mycobacterial immune reconstitution inflammatory syndrome (IRIS) in patients with HIV-1 infection result from immunopathology that is characterized by increased production of multiple pro-inflammatory chemokines and cytokines associated with activation of myeloid cells (monocytes, macrophages and neutrophils). We propose that both conditions arise because innate immune responses generated in the absence of effective adaptive immune responses lead to monocyte/macrophage activation that is amplified by the emergence of a pathogen-specific adaptive immune response skewed towards monocyte/macrophage activating activity by the immunomodulatory effects of cytokines produced during the innate response, particularly interleukin-18. In mycobacterial IRIS, that disease-enhancing immune response is dominated by a Th1 CD4+ T cell response against mycobacterial antigens. By analogy, it is proposed that in severe COVID-19, amplification of monocyte/macrophage activation results from the effects of a SARS-CoV-2 spike protein antibody response with pro-inflammatory characteristics, including high proportions of IgG3 and IgA2 antibodies and afucosylation of IgG1 antibodies, that arises from B cell differentiation in an extra-follicular pathway promoted by activation of mucosa-associated invariant T cells. We suggest that therapy for the hyperinflammation underlying both COVID-19 and mycobacterial IRIS might be improved by targeting the immunomodulatory as well as the pro-inflammatory effects of the 'cytokine storm'.


Assuntos
/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Síndrome Inflamatória da Reconstituição Imune/imunologia , /imunologia , Humanos , Imunidade Inata , Ativação de Macrófagos , Macrófagos/imunologia , Monócitos/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Células Th1/imunologia
10.
BMC Surg ; 21(1): 178, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794850

RESUMO

BACKGROUND: The inflammation indexes in blood routine play an essential role in evaluating the prognosis of patients with hepatocellular carcinoma, but the effect on early recurrence has not been clarified. The study aimed to investigate the risk factors of early recurrence (within 2 years) and recurrence-free survival after curative hepatectomy and explore the role of inflammatory indexes in predicting early recurrence. METHODS: The baseline data of 161 patients with hepatocellular carcinoma were analyzed retrospectively. The optimal cut-off value of the inflammatory index was determined according to the Youden index. Its predictive performance was compared by the area under the receiver operating characteristic curve. Logistic and Cox regression analyses were used to determine the risk factors of early recurrence and recurrence-free survival. RESULTS: The area under the curve of monocyte to lymphocyte ratio (MLR) for predicting early recurrence was 0.700, which was better than systemic inflammatory response index (SIRI), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and systemic immune-inflammatory index (SII). MLR, tumour size, tumour differentiation and BCLC stage are all risk factors for early recurrence and recurrence-free survival of HCC. Combining the above four risk factors to construct a joint index, the area under the curve for predicting early recurrence was 0.829, which was better than single MLR, tumour size, tumour differentiation and BCLC stage. Furthermore, with the increase of risk factors, the recurrence-free survival of patients is worse. CONCLUSION: The combination of MLR and clinical risk factors is helpful for clinicians to identify high-risk patients with early recurrence and carry out active postoperative adjuvant therapy to improve the prognosis of patients.


Assuntos
Carcinoma Hepatocelular , Hepatectomia , Inflamação , Neoplasias Hepáticas , Recidiva Local de Neoplasia , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/cirurgia , Humanos , Inflamação/sangue , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/cirurgia , Contagem de Linfócitos , Monócitos , Recidiva Local de Neoplasia/sangue , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco
12.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(3): 322-327, 2021 Mar 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-33927081

RESUMO

Chronic myeloid leukemia with a significant increase of monocytes is rare and difficult to identify from chronic myelo-monocytic leukemia in clinic. A 31-year-old male patient with systemic pain was initially diagnosed as chronic myelo-monocytic leukemia, who was finally diagnosed as chronic myeloid leukemia by fusion gene and chromosome examination. In addition to the typical Ph chromosome, a rare chromosome translocation t(2; 7)(p13; p22) was observed. The detection of monocyte subsets by multi-parameter flow cytometry is a diagnostic marker to distinguish the above 2 diseases. The relationship between fusion genes and mononucleosis is not clear. Tyrosine kinase inhibitors or allogeneic hematopoietic stem cell transplantation can be used in the treatment for this disease.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Monócitos , Adulto , Humanos , Cariótipo , Cariotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Translocação Genética
13.
J Immunother Cancer ; 9(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33837054

RESUMO

The ongoing pandemic caused by the novel coronavirus SARS-CoV-2 has disrupted the global economy and strained healthcare systems to their limits. After the virus first emerged in late 2019, the first intervention that demonstrated significant reductions in mortality for severe COVID-19 in large-scale trials was corticosteroids. Additional options that may reduce the burden on the healthcare system by reducing the number of patients requiring intensive care unit support are desperately needed, yet no therapy has conclusively established benefit in randomized studies for the management of moderate or mild cases of disease. Severe COVID-19 disease is characterized by a respiratory distress syndrome accompanied by elevated levels of several systemic cytokines, in a profile that shares several features with known inflammatory pathologies such as hemophagocytic lymphohistiocytosis and cytokine release syndrome secondary to chimeric antigen receptor (CAR) T cell therapy. Based on these observations, modulation of inflammatory cytokines, particularly interleukin (IL)-6, was proposed as a strategy to mitigate severe disease. Despite encouraging recoveries with anti-IL-6 agents, especially tocilizumab from single-arm studies, early randomized trials returned mixed results in terms of clinical benefit with these interventions. Later, larger trials such as RECOVERY and REMAP-CAP, however, are establishing anti-IL-6 in combination with steroids as a potential option for hypoxic patients with evidence of hyperinflammation. We propose that a positive feedback loop primarily mediated by macrophages and monocytes initiates the inflammatory cascade in severe COVID-19, and thus optimal benefit with anti-IL-6 therapies may require intervention during a finite window of opportunity at the outset of hyperinflammation but before fulminant disease causes irreversible tissue damage-as defined clinically by C reactive protein levels higher than 75 mg/L.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Interleucina-6/antagonistas & inibidores , /isolamento & purificação , /epidemiologia , Citocinas/imunologia , Citocinas/metabolismo , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Interleucina-6/imunologia , Interleucina-6/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Monócitos/metabolismo , Pandemias , /fisiologia
14.
Nat Commun ; 12(1): 2147, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846309

RESUMO

Tissue mononuclear phagocytes (MNP) are specialised in pathogen detection and antigen presentation. As such they deliver HIV to its primary target cells; CD4 T cells. Most MNP HIV transmission studies have focused on epithelial MNPs. However, as mucosal trauma and inflammation are now known to be strongly associated with HIV transmission, here we examine the role of sub-epithelial MNPs which are present in a diverse array of subsets. We show that HIV can penetrate the epithelial surface to interact with sub-epithelial resident MNPs in anogenital explants and define the full array of subsets that are present in the human anogenital and colorectal tissues that HIV may encounter during sexual transmission. In doing so we identify two subsets that preferentially take up HIV, become infected and transmit the virus to CD4 T cells; CD14+CD1c+ monocyte-derived dendritic cells and langerin-expressing conventional dendritic cells 2 (cDC2).


Assuntos
Canal Anal/citologia , Antígenos CD/metabolismo , Células Dendríticas/metabolismo , Genitália/citologia , HIV-1/fisiologia , Lectinas Tipo C/metabolismo , Lectinas de Ligação a Manose/metabolismo , Monócitos/metabolismo , Linfócitos T CD4-Positivos/imunologia , Forma Celular , Colagenases/metabolismo , Derme/metabolismo , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Receptores de Lipopolissacarídeos/metabolismo , Membrana Mucosa/metabolismo , Fagócitos/metabolismo , Fenótipo , Receptores CCR5/metabolismo , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Transcrição Genética
15.
Infez Med ; 29(1): 46-53, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33664172

RESUMO

Direct viral damage and uncontrolled inflammation contribute to disease severity in SARS-CoV-2 infection. The aim of this study was to investigate the prognostic significance of neutrophil-to-lymphocyte [NLR], lymphocyte-to-monocyte [LMR] and platelet-to-lymphocyte [PLR] ratios in COVID-19 patients. All 184 COVID-19 patients hospitalized in our institution between March - April 2020 were retrospectively analyzed. The patients were grouped into intubated and non-intubated, and subgrouped into survived and deceased. An unpaired Student's t-test was used for continuous variables, and the Pearson Chi-square (χ2) test for categorical. Univariate and multivariate logistic regression models were developed to assess the independent relationship between NLR, LMR and PLR and unfavorable outcomes. Non-parametric correlations were calculated using Spearman's Rho correlation coefficient. The mean age of the patients was 64.7; mean BMI was 29.10; 73 (39.67%) were female and 111 male (60.33%). No statistical difference between groups was identified with regard to NLR (mean 8.29, standard deviation [SD] 7.86). On multivariate regression analysis, only PLR and LMR were shown to influence the ratio and it was positively correlated with PLR, lactate and C-reactive protein [CRP]. LMR for non-intubated survived [NI-S] (mean 2.29, SD 1.31) and non-intubated deceased [NI-D] (mean 1.79, SD 0.81) groups were statistically significant (p=0.03). LMR was influenced only by NLR on regression analysis. A positive correlation of LMR with body mass index [BMI] was ascertained. No statistical significance was found between groups for PLR (mean 269.85, SD 207.98) and the ratio was influenced by age and NLR on regression analysis, and positively correlated with NLR. To conclude, previously reported findings of a prognostic role of NLR, LMR and PLR in COVID-19 were not validated in our cohort and we would caution against using the ratios in question as independent markers for disease severity.


Assuntos
Plaquetas , Linfócitos , Monócitos , Neutrófilos , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Feminino , Humanos , Intubação Intratraqueal/mortalidade , Ácido Láctico/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
16.
Int J Mol Sci ; 22(5)2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33670902

RESUMO

Given its uniformly high expression on plasma cells, CD38 has been considered as a therapeutic target in patients with systemic lupus erythematosus (SLE). Herein, we investigate the distribution of CD38 expression by peripheral blood leukocyte lineages to evaluate the potential therapeutic effect of CD38-targeting antibodies on these immune cell subsets and to delineate the use of CD38 as a biomarker in SLE. We analyzed the expression of CD38 on peripheral blood leukocyte subsets by flow and mass cytometry in two different cohorts, comprising a total of 56 SLE patients. The CD38 expression levels were subsequently correlated across immune cell lineages and subsets, and with clinical and serologic disease parameters of SLE. Compared to healthy controls (HC), CD38 expression levels in SLE were significantly increased on circulating plasmacytoid dendritic cells, CD14++CD16+ monocytes, CD56+ CD16dim natural killer cells, marginal zone-like IgD+CD27+ B cells, and on CD4+ and CD8+ memory T cells. Correlation analyses revealed coordinated CD38 expression between individual innate and memory T cell subsets in SLE but not HC. However, CD38 expression levels were heterogeneous across patients, and no correlation was found between CD38 expression on immune cell subsets and the disease activity index SLEDAI-2K or established serologic and immunological markers of disease activity. In conclusion, we identified widespread changes in CD38 expression on SLE immune cells that highly correlated over different leukocyte subsets within individual patients, but was heterogenous within the population of SLE patients, regardless of disease severity or clinical manifestations. As anti-CD38 treatment is being investigated in SLE, our results may have important implications for the personalized targeting of pathogenic leukocytes by anti-CD38 monoclonal antibodies.


Assuntos
ADP-Ribosil Ciclase 1/genética , Regulação da Expressão Gênica , Leucócitos/metabolismo , Lúpus Eritematoso Sistêmico/genética , Glicoproteínas de Membrana/genética , Adulto , Feminino , Citometria de Fluxo , Humanos , Células Matadoras Naturais , Lúpus Eritematoso Sistêmico/enzimologia , Masculino , Pessoa de Meia-Idade , Monócitos , Subpopulações de Linfócitos T , Adulto Jovem
17.
Immunity ; 54(4): 797-814.e6, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33765436

RESUMO

Immune response dynamics in coronavirus disease 2019 (COVID-19) and their severe manifestations have largely been studied in circulation. Here, we examined the relationship between immune processes in the respiratory tract and circulation through longitudinal phenotypic, transcriptomic, and cytokine profiling of paired airway and blood samples from patients with severe COVID-19 relative to heathy controls. In COVID-19 airways, T cells exhibited activated, tissue-resident, and protective profiles; higher T cell frequencies correlated with survival and younger age. Myeloid cells in COVID-19 airways featured hyperinflammatory signatures, and higher frequencies of these cells correlated with mortality and older age. In COVID-19 blood, aberrant CD163+ monocytes predominated over conventional monocytes, and were found in corresponding airway samples and in damaged alveoli. High levels of myeloid chemoattractants in airways suggest recruitment of these cells through a CCL2-CCR2 chemokine axis. Our findings provide insights into immune processes driving COVID-19 lung pathology with therapeutic implications for targeting inflammation in the respiratory tract.


Assuntos
/imunologia , Pulmão/imunologia , Células Mieloides/imunologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , /mortalidade , Citocinas/imunologia , Citocinas/metabolismo , Humanos , Inflamação , Estudos Longitudinais , Pulmão/patologia , Macrófagos/imunologia , Macrófagos/patologia , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/patologia , Células Mieloides/patologia , Linfócitos T/imunologia , Linfócitos T/patologia , Transcriptoma , Adulto Jovem
18.
Methods Mol Biol ; 2265: 119-128, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704710

RESUMO

Tumor-associated macrophages (TAMs) are one of most important components of the tumor microenvironment. Although many assays have been developed to differentiate monocytes into macrophages (Mϕ) for studying the biology of TAMs in vitro, little is known whether the macrophages induced by these approaches can recapitulate the biology of TAMs present in the tumor microenvironment. We have developed a novel assay to differentiate human monocytes into TAMs using modified melanoma-conditioned medium, which is derived from the concentrated tumor cell culture medium. Characterization of these modified melanoma-conditioned medium-induced macrophages (MCMI-Mϕ) by multiple flow cytometry, Luminex, microarray, and immunohistochemistry analyses indicates that MCMI-Mϕ are phenotypically and functionally highly similar to the TAMs present in the tumor microenvironment.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Macrófagos/citologia , Melanoma/metabolismo , Técnicas de Cultura de Células/métodos , Linhagem Celular Tumoral , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Melanoma/patologia , Monócitos/citologia , Monócitos/efeitos dos fármacos , Microambiente Tumoral
19.
Nat Commun ; 12(1): 1717, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741967

RESUMO

Myeloid-derived suppressor cells (MDSC) are pathologically activated neutrophils and monocytes with potent immune suppressive activity. These cells play an important role in accelerating tumor progression and undermining the efficacy of anti-cancer therapies. The natural mechanisms limiting MDSC activity are not well understood. Here, we present evidence that type I interferons (IFN1) receptor signaling serves as a universal mechanism that restricts acquisition of suppressive activity by these cells. Downregulation of the IFNAR1 chain of this receptor is found in MDSC from cancer patients and mouse tumor models. The decrease in IFNAR1 depends on the activation of the p38 protein kinase and is required for activation of the immune suppressive phenotype. Whereas deletion of IFNAR1 is not sufficient to convert neutrophils and monocytes to MDSC, genetic stabilization of IFNAR1 in tumor bearing mice undermines suppressive activity of MDSC and has potent antitumor effect. Stabilizing IFNAR1 using inhibitor of p38 combined with the interferon induction therapy elicits a robust anti-tumor effect. Thus, negative regulatory mechanisms of MDSC function can be exploited therapeutically.


Assuntos
Interferon Tipo I/metabolismo , Células Supressoras Mieloides/imunologia , Neoplasias/metabolismo , Receptor de Interferon alfa e beta/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antineoplásicos/farmacologia , Medula Óssea , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Monócitos/imunologia , Neutrófilos/imunologia , Receptor de Interferon alfa e beta/genética , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
20.
Nat Commun ; 12(1): 1742, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741975

RESUMO

A highly protective vaccine will greatly facilitate achieving and sustaining malaria elimination. Understanding mechanisms of antibody-mediated immunity is crucial for developing vaccines with high efficacy. Here, we identify key roles in humoral immunity for Fcγ-receptor (FcγR) interactions and opsonic phagocytosis of sporozoites. We identify a major role for neutrophils in mediating phagocytic clearance of sporozoites in peripheral blood, whereas monocytes contribute a minor role. Antibodies also promote natural killer cell activity. Mechanistically, antibody interactions with FcγRIII appear essential, with FcγRIIa also required for maximum activity. All regions of the circumsporozoite protein are targets of functional antibodies against sporozoites, and N-terminal antibodies have more activity in some assays. Functional antibodies are slowly acquired following natural exposure to malaria, being present among some exposed adults, but uncommon among children. Our findings reveal targets and mechanisms of immunity that could be exploited in vaccine design to maximize efficacy.


Assuntos
Imunidade Humoral , Malária/imunologia , Malária/prevenção & controle , Receptores de IgG/imunologia , Esporozoítos/imunologia , Adulto , Idoso , Anticorpos Antiprotozoários/imunologia , Criança , Feminino , Humanos , Quênia , Vacinas Antimaláricas/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Neutrófilos/imunologia , Fagocitose/imunologia , Plasmodium falciparum/imunologia , Receptores de IgG/metabolismo , Células THP-1 , Adulto Jovem
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