Microbiology & Immunology - Research Publications

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    A Novel Whole Blood Assay Detects Flagellin-Specific CD4+ T Cells in Patients with Inflammatory Bowel Disease
    Cook, L ; Wong, MQ ; Garcia, R ; Himmel, ME ; Bressler, B ; Seidman, EG ; Steiner, TS ; Levings, MK (W B Saunders Co-Elsevier, 2017-04-01)
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    High-dimensional Analysis of Human Regulatory T Cells Using Mass Cytometry
    Dawson, N ; Cook, L ; Pesenacker, A ; Hoeppli, R ; Morishita, K ; Broady, R ; Levings, MK (American Association of Immunologists, 2016-05-01)
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    Dock8 Regulates Lymphocyte Shape Integrity For Skin Antiviral Responses
    Zhang, Q ; Dove, C ; Strauss-Albee, D ; Garcia, J ; Mandl, J ; Grodick, R ; Jing, H ; Chandler-Brown, D ; Kim, E ; Murdock, HM ; Crawford, GH ; Matthews, H ; Freeman, AF ; Cornall, R ; Germain, R ; Mueller, SN ; Su, H (SPRINGER/PLENUM PUBLISHERS, 2014-04)
    DOCK8 mutations result in an inherited combined immunodeficiency characterized by increased susceptibility to skin and other infections. We show that when DOCK8-deficient T and NK cells migrate through confined spaces, they develop cell shape and nuclear deformation abnormalities that do not impair chemotaxis but contribute to a distinct form of catastrophic cell death we term cytothripsis. Such defects arise during lymphocyte migration in collagen-dense tissues when DOCK8, through CDC42 and p21-activated kinase (PAK), is unavailable to coordinate cytoskeletal structures. Cytothripsis of DOCK8-deficient cells prevents the generation of long-lived skin-resident memory CD8 T cells, which in turn impairs control of herpesvirus skin infections. Our results establish that DOCK8-regulated shape integrity of lymphocytes prevents cytothripsis and promotes antiviral immunity in the skin.
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    Spatial and temporal dynamics of dengue in southern Vietnam
    Cuong, HQ ; Thai, K ; Boni, M ; Rabaa, M ; Vu, NT ; Quang, LC ; Huu, TN ; Cazelles, B ; Simmons, C ; Anders, K (ELSEVIER SCI LTD, 2012-06)
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    Microvascular and endothelial function for risk prediction in dengue: an observational study
    Yacoub, S ; Wertheim, H ; Simmons, CP ; Screaton, G ; Wills, B (ELSEVIER SCIENCE INC, 2015-02-26)
    BACKGROUND: Dengue infection can result in a wide spectrum of disease. The defining feature of severe disease is increased capillary permeability, which can lead to hypovolaemic shock. Microvascular and endothelial dysfunction might underlie hypovolaemic shock, but they have not been assessed clinically. We aimed to investigate the use of microvascular assessment as a prognostic method in dengue. METHODS: This is an ongoing prospective observational study that aims to recruit 300 participants: children over the age of 3 years and adults presenting to two outpatient departments in Vietnam with fever of less than 72 h duration and suspected dengue, and patients admitted to hospital with warning signs or severe disease. Participants are being clinically assessed daily for 6 days, and 2 weeks later. Microvascular imaging using sublingual sidestream darkfield imaging (SDF) and endothelial function testing using peripheral artery tonometry are being performed at enrolment, defervescence, and follow-up FINDINGS: To date, 167 patients have been recruited (92 outpatient arm, 75 inpatient arm, median age 27 years [IQR 21-33], 78 male [47%]). Dengue has been confirmed in 67 individuals in the outpatient arm, of whom 29 (43%) developed warning signs, three (4%) developed severe disease, and 35 had uncomplicated dengue; the other 25 outpatients (27%) were diagnosed as other febrile illness. At enrolment, the reactive hyperaemic index, a marker of endothelial function, was lowest in the patients who went on to develop severe dengue (median 1·54, IQR 1·36-1·77) followed by those who developed warning signs (1·78, 1·43-2·36) and then uncomplicated dengue (2·18, 1·65-2·24). Initial SDF results showed a lower proportion of perfused vessels and mean flow index during the febrile phase of dengue compared with follow-up, and were worst in the severe group at defervescence. INTERPRETATION: This study of vascular function at serial timepoints in dengue is, to our knowledge, the first and most comprehensive. Our preliminary results suggest that microvascular and endothelial dysfunction are associated with severity of dengue, and occur before the appearance of severe clinical manifestations. These techniques might be useful in risk prediction in dengue. A limitation is that a formal sample size could not be calculated because no previous microvascular data in dengue exist. FUNDING: Wellcome Trust.