ORCID Profile
0000-0002-4158-2241
Current Organisations
Center of Biomedical Research
,
University of Bristol
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Publications
Association of systemic vitamin D on the course of dengue virus infection in adults: a single-centre dengue cohort study at a large institution in Singapore
Publisher: Medknow
Date: 02-06-2022
Abstract: Introduction: Host immune responses may impact dengue severity in adults. Vitamin D has multiple immunomodulatory effects on innate and adaptive immunity. Methods: We evaluated the association between systemic 25-hydroxyvitamin D [25-(OH) D] and dengue disease severity in adults. We measured plasma for total 25-(OH) D levels with an electrochemiluminescence immunoassay using stored s les from participants with laboratory confirmed dengue who were prospectively enrolled in 2012–2016 at our institution. Results: 80 participants (median age 43 years) were enrolled. Six participants had severe dengue based on the World Health Organisation (WHO) 1997 criteria (i.e. dengue haemorrhagic fever/dengue shock syndrome) and another six had severe dengue based on the WHO 2009 criteria. Median 25-(OH) D at acute phase of dengue was 6.175 µg/L (interquartile range 3.82–8.21 range 3.00–15.29) in all participants. 25-(OH) D showed inverse linear trend with severe dengue manifestations based on the WHO 2009 criteria (aRR 0.72 95% confidence interval 0.57–0.91 p 0.01) after adjustment for age, gender and ethnicity. Conclusion: Limited studies have evaluated the role of systemic 25-(OH) D on dengue severity. Our study found low systemic 25-(OH) D was associated with increased dengue disease severity, particularly for severe bleeding that was not explained by thrombocytopenia. Further studies investigating the underlying immune mechanisms and effects on the vascular endothelium are needed.
Modulating the Delivery of 5-Fluorouracil to Human Colon Cancer Cells Using Multifunctional Arginine-Coated Manganese Oxide Nanocuboids with MRI Properties
Publisher: American Chemical Society (ACS)
Date: 02-09-2020
Abstract: 5-Fluorouracil (5-FU) is one of the most prescribed drugs and the major component of chemotherapy for the treatment of colorectal cancer. In this study, we have designed arginine-functionalized manganese oxide nanocuboids (Arg@MNCs) for the effective delivery of 5-FU to colon cancer cells. Arginine was used as multifunctional agent to provide stability to MNCs, achieve high drug loading, control the release of loaded drug, and improve delivery to cancer cells. The synthesized Arg@MNCs were characterized by DLS, TEM, XRD, FTIR, XPS, TGA, and VSM analysis. The structural and morphological analysis by TEM showed cuboid-shaped MNCs with average particle size ∼15 nm. Biodegradation studies indicated that the Arg@MNCs were degraded at endolyosomal pH in 24 h while remaining stable at physiological pH. Hemolytic toxicity studies revealed the safety and nontoxic nature of the prepared MNCs. 5-FU-loaded Arg@MNCs showed significant control over the release of 5-FU, decrease in the hemolytic toxicity of loaded 5-FU but higher in vitro anticancer activity against HCT 116 and SW480 human colon cancer cells. Importantly, both the bare MNCs and Arg@MNCs showed excellent T1 and T2MR relaxivity under 3.0 T MRI scanner. Thus, the nanostructures developed in this study, i.e., 5-FU-Arg@MNCs could overcome the issues of both MNCs (stability) and 5-FU (low drug loading and nonspecificity) and may be used as a multifunctional theranostic nanocarrier for colon cancer treatment.
NK cells are activated and primed for skin-homing during acute dengue virus infection in humans
Publisher: Springer Science and Business Media LLC
Date: 29-08-2019
DOI: 10.1038/S41467-019-11878-3
Abstract: Despite animal models showing that natural killer (NK) cells are important players in the early defense against many viral infections, the NK cell response is poorly understood in humans. Here we analyze the phenotype, temporal dynamics, regulation and trafficking of NK cells in a patient cohort with acute dengue virus infection. NK cells are robustly activated and proliferate during the first week after symptom debut. Increased IL-18 levels in plasma and in induced skin blisters of DENV-infected patients, as well as concomitant signaling downstream of the IL-18R, suggests an IL-18-dependent mechanism in driving the proliferative NK cell response. Responding NK cells have a less mature phenotype and a distinct chemokine-receptor imprint indicative of skin-homing. A corresponding NK cell subset can be localized to skin early during acute infection. These data provide evidence of an IL-18-driven NK cell proliferation and priming for skin-homing during an acute viral infection in humans.
Differential Targeting of Viral Components by CD4+versus CD8+T Lymphocytes in Dengue Virus Infection
Publisher: American Society for Microbiology
Date: 03-2013
DOI: 10.1128/JVI.02675-12
Abstract: Dengue virus (DENV) is the principal arthropod-borne viral pathogen afflicting human populations. While repertoires of antibodies to DENV have been linked to protection or enhanced infection, the role of T lymphocytes in these processes remains poorly defined. This study provides a comprehensive overview of CD4 + and CD8 + T cell epitope reactivities against the DENV 2 proteome in adult patients experiencing secondary DENV infection. Dengue virus-specific T cell responses directed against an overlapping 15mer peptide library spanning the DENV 2 proteome were analyzed ex vivo by enzyme-linked immunosorbent spot assay, and recognition of in idual peptides was further characterized in specific T cell lines. Thirty novel T cell epitopes were identified, 9 of which are CD4 + and 21 are CD8 + T cell epitopes. We observe that whereas CD8 + T cell epitopes preferentially target nonstructural proteins (NS3 and NS5), CD4 + epitopes are skewed toward recognition of viral components that are also targeted by B lymphocytes (envelope, capsid, and NS1). Consistently, a large proportion of dengue virus-specific CD4 + T cells have phenotypic characteristics of circulating follicular helper T cells (CXCR5 expression and production of interleukin-21 or gamma interferon), suggesting that they are interacting with B cells in vivo . This study shows that during a dengue virus infection, the protein targets of human CD4 + and CD8 + T cells are largely distinct, thus highlighting key differences in the immunodominance of DENV proteins for these two cell types. This has important implications for our understanding of how the two arms of the human adaptive immune system are differentially targeted and employed as part of our response to DENV infection.
Cross-Reactivity and Anti-viral Function of Dengue Capsid and NS3-Specific Memory T Cells Toward Zika Virus
Publisher: Frontiers Media SA
Date: 10-2018
Hepatitis B virus–specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation
Publisher: American Society for Clinical Investigation
Date: 08-01-2018
DOI: 10.1172/JCI92812
Virus-specific T lymphocytes home to the skin during natural dengue infection
Publisher: American Association for the Advancement of Science (AAAS)
Date: 11-03-2015
DOI: 10.1126/SCITRANSLMED.AAA0526
Abstract: Circulating virus-specific T lymphocytes may contribute to immune surveillance against dengue in the skin.
Large-Scale HLA Tetramer Tracking of T Cells during Dengue Infection Reveals Broad Acute Activation and Differentiation into Two Memory Cell Fates
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.IMMUNI.2019.10.007
Abstract: T cells play important multifaceted roles during dengue infection, and understanding their responses is important for defining correlates of protective immunity and identifying effective vaccine antigens. Using mass cytometry and a highly multiplexed peptide-HLA (human leukocyte antigen) tetramer staining strategy, we probed T cells from dengue patients-a total of 430 dengue and control candidate epitopes-together with key markers of activation, trafficking, and differentiation. During acute disease, dengue-specific CD8
Related Organisations
University Of Bristol
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for Anupam Guleria.