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4 results on '"Stylianou E"'

1. Corrigendum: T-cell activation is an immune correlate of risk in BCG vaccinated infants

Author

Fletcher, H, Snowden, M, Landry, B, Rida, W, Satti, I, Harris, S, Matsumiya, M, Tanner, R, O'Shea, M, Dheenadhayalan, V, Bogardus, L, Stockdale, L, Marsay, L, Chomka, A, Harrington-Kandt, R, Manjaly Thomas, Z, Naranbhai, V, Stylianou, E, Darboe, F, Penn-Nicholson, A, Nemes, E, Hatheril, M, Hussey, G, Mahomed, H, Tameris, M, McClain, J, Evans, T, Hanekom, W, Scriba, T, and McShane, H

Subjects
CD4-Positive T-Lymphocytes, Time Factors, Adolescent, Vaccination, Immunity, Infant, HLA-DR Antigens, Mycobacterium tuberculosis, Lymphocyte Activation, Corrigenda, Article, Cohort Studies, Placebos, Logistic Models, Risk Factors, Case-Control Studies, Immunoglobulin G, Antibody Formation, BCG Vaccine, Vaccines, DNA, Humans, Tuberculosis, Tuberculosis Vaccines
Abstract

Vaccines to protect against tuberculosis (TB) are urgently needed. We performed a case–control analysis to identify immune correlates of TB disease risk in Bacille Calmette–Guerin (BCG) immunized infants from the MVA85A efficacy trial. Among 53 TB case infants and 205 matched controls, the frequency of activated HLA-DR+ CD4+ T cells associates with increased TB disease risk (OR=1.828, 95% CI=1.25–2.68, P=0.002, FDR=0.04, conditional logistic regression). In an independent study of Mycobacterium tuberculosis-infected adolescents, activated HLA-DR+ CD4+ T cells also associate with increased TB disease risk (OR=1.387, 95% CI=1.068–1.801, P=0.014, conditional logistic regression). In infants, BCG-specific T cells secreting IFN-γ associate with reduced risk of TB (OR=0.502, 95% CI=0.29–0.86, P=0.013, FDR=0.14). The causes and impact of T-cell activation on disease risk should be considered when designing and testing TB vaccine candidates for these populations., BCG vaccine confers only partial protection against tuberculosis. Here the authors show that the risk of tuberculosis infection and progression to disease in BCG-immunized children positively correlates with the frequency of activated HLA-DR+CD4+ T cells.

Published
2016

2. Regulation of mycobacterial infection by macrophage Gch1 and tetrahydrobiopterin.

Author

McNeill E, Stylianou E, Crabtree MJ, Harrington-Kandt R, Kolb AL, Diotallevi M, Hale AB, Bettencourt P, Tanner R, O'Shea MK, Matsumiya M, Lockstone H, Müller J, Fletcher HA, Greaves DR, McShane H, and Channon KM

Subjects
Animals, Biopterins genetics, Biopterins metabolism, Biopterins physiology, Cell Survival, GTP Cyclohydrolase genetics, GTP Cyclohydrolase metabolism, Gene Deletion, Gene Expression Profiling, Humans, Macrophages metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Nitric Oxide Synthase Type II genetics, Nitric Oxide Synthase Type II metabolism, Biopterins analogs & derivatives, GTP Cyclohydrolase physiology, Nitric Oxide biosynthesis, Nitric Oxide Synthase Type II physiology, Tuberculosis immunology
Abstract

Inducible nitric oxide synthase (iNOS) plays a crucial role in controlling growth of Mycobacterium tuberculosis (M.tb), presumably via nitric oxide (NO) mediated killing. Here we show that leukocyte-specific deficiency of NO production, through targeted loss of the iNOS cofactor tetrahydrobiopterin (BH4), results in enhanced control of M.tb infection; by contrast, loss of iNOS renders mice susceptible to M.tb. By comparing two complementary NO-deficient models, Nos2 -/- mice and BH4 deficient Gch1 fl/fl Tie2cre mice, we uncover NO-independent mechanisms of anti-mycobacterial immunity. In both murine and human leukocytes, decreased Gch1 expression correlates with enhanced cell-intrinsic control of mycobacterial infection in vitro. Gene expression analysis reveals that Gch1 deficient macrophages have altered inflammatory response, lysosomal function, cell survival and cellular metabolism, thereby enhancing the control of bacterial infection. Our data thus highlight the importance of the NO-independent functions of Nos2 and Gch1 in mycobacterial control.

Published
2018
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3. T-cell activation is an immune correlate of risk in BCG vaccinated infants.

Author

Fletcher HA, Snowden MA, Landry B, Rida W, Satti I, Harris SA, Matsumiya M, Tanner R, O'Shea MK, Dheenadhayalan V, Bogardus L, Stockdale L, Marsay L, Chomka A, Harrington-Kandt R, Manjaly-Thomas ZR, Naranbhai V, Stylianou E, Darboe F, Penn-Nicholson A, Nemes E, Hatherill M, Hussey G, Mahomed H, Tameris M, McClain JB, Evans TG, Hanekom WA, Scriba TJ, and McShane H

Subjects
Adolescent, Antibody Formation immunology, Case-Control Studies, Cohort Studies, HLA-DR Antigens immunology, Humans, Immunity, Immunoglobulin G immunology, Infant, Logistic Models, Mycobacterium tuberculosis immunology, Placebos, Risk Factors, Time Factors, Tuberculosis blood, Tuberculosis immunology, Tuberculosis Vaccines immunology, Vaccines, DNA, BCG Vaccine immunology, CD4-Positive T-Lymphocytes immunology, Lymphocyte Activation immunology, Vaccination
Abstract

Vaccines to protect against tuberculosis (TB) are urgently needed. We performed a case-control analysis to identify immune correlates of TB disease risk in Bacille Calmette-Guerin (BCG) immunized infants from the MVA85A efficacy trial. Among 53 TB case infants and 205 matched controls, the frequency of activated HLA-DR(+) CD4(+) T cells associates with increased TB disease risk (OR=1.828, 95% CI=1.25-2.68, P=0.002, FDR=0.04, conditional logistic regression). In an independent study of Mycobacterium tuberculosis-infected adolescents, activated HLA-DR(+) CD4(+) T cells also associate with increased TB disease risk (OR=1.387, 95% CI=1.068-1.801, P=0.014, conditional logistic regression). In infants, BCG-specific T cells secreting IFN-γ associate with reduced risk of TB (OR=0.502, 95% CI=0.29-0.86, P=0.013, FDR=0.14). The causes and impact of T-cell activation on disease risk should be considered when designing and testing TB vaccine candidates for these populations.

Published
2016
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4. RGS1 regulates myeloid cell accumulation in atherosclerosis and aortic aneurysm rupture through altered chemokine signalling.

Author

Patel J, McNeill E, Douglas G, Hale AB, de Bono J, Lee R, Iqbal AJ, Regan-Komito D, Stylianou E, Greaves DR, and Channon KM

Subjects
Animals, Aorta metabolism, Aortic Aneurysm genetics, Blood Pressure, Bone Marrow Transplantation, Chemotaxis, Flow Cytometry, Humans, Inflammation, Leukocytes cytology, Leukocytes metabolism, Macrophages cytology, Macrophages metabolism, Male, Mice, Mice, Knockout, Monocytes cytology, Receptors, Chemokine metabolism, Vascular Diseases metabolism, Aortic Aneurysm metabolism, Atherosclerosis metabolism, Chemokines metabolism, RGS Proteins metabolism, Signal Transduction
Abstract

Chemokine signalling drives monocyte recruitment in atherosclerosis and aortic aneurysms. The mechanisms that lead to retention and accumulation of macrophages in the vascular wall remain unclear. Regulator of G-Protein Signalling-1 (RGS1) deactivates G-protein signalling, reducing the response to sustained chemokine stimulation. Here we show that Rgs1 is upregulated in atherosclerotic plaque and aortic aneurysms. Rgs1 reduces macrophage chemotaxis and desensitizes chemokine receptor signalling. In early atherosclerotic lesions, Rgs1 regulates macrophage accumulation and is required for the formation and rupture of Angiotensin II-induced aortic aneurysms, through effects on leukocyte retention. Collectively, these data reveal a role for Rgs1 in leukocyte trafficking and vascular inflammation and identify Rgs1, and inhibition of chemokine receptor signalling as potential therapeutic targets in vascular disease.

Published
2015
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