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1.
Viral Immunol ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38808464

RESUMO

Human pegivirus (HPgV) appears to alter the prognosis of HIV disease by modulating T cell homeostasis, chemokine/cytokine production, and T cell activation. In this study, we evaluated if HPgV had any 'favorable' impact on the quantity and quality of T cells in HIV-infected individuals. T cell subsets such as CD4lo, CD4hi, and CD8+ T cells, CD4+ MAIT cells, CD8+ MAIT cells, follicular helper T (TFH) cells, and follicular cytotoxic T (TFC) cells were characterized based on the expression of markers associated with immune activation (CD69, ICOS), proliferation (ki67), cytokine production (TNF-α, IFN-γ), and exhaustion (PD-1). HIV+HPgV+ individuals had lower transaminase SGOT (liver) and GGT (biliary) in the plasma than those who were HPgV-. HIV/HPgV coinfection was significantly associated with increased absolute CD4+ T cell counts. HIV+HPgV+ and HIV+HPgV- individuals had highly activated T cell subsets with high expression of CD69 and ICOS on bulk CD4+ and CD8+ T cells, CD4+ MAIT cells, CD8+ MAIT cells, and CXCR5+CD4+ T cells and CXCR5+CD8+ T cells compared with healthy controls. Irrespective of immune activation markers, these cells also displayed higher levels of PD-1 on CD4+ T and CD8+ T cells . Exploring effector functionality based on mitogen stimulation demonstrated increased cytokine production by CD4+ MAIT and CD8+ MAIT cells. Decrease in absolute CD4+ T cell counts correlated positively with intracellular IFN-γ levels by CD4lo T cells, whereas increase of the same correlated negatively with TNF-α in the CD4lo T cells of HIV+HPgV+ individuals. HIV/HPgV coinfected individuals display functional CD4+ and CD8+ MAIT, TFH, and TFC cells irrespective of PD-1 expression.

2.
medRxiv ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38699322

RESUMO

In December 2023, we observed a notable shift in the COVID-19 landscape, when the JN.1 emerged as a predominant SARS-CoV-2 variant with a 95% incidence. We characterized the clinical profile, and genetic changes in JN.1, an emerging SARS-CoV-2 variant of interest. Whole genome sequencing was performed on SARS-CoV-2 positive samples, followed by sequence analysis. Mutations within the spike protein sequences were analyzed and compared with the previous lineages and sublineages of SARS-CoV-2, to identify the potential impact of these unique mutations on protein structure and possible functionality. Several unique and dynamic mutations were identified herein. Our data provides key insights into the emergence of newer variants of SARS-CoV-2 in our region and highlights the need for robust and sustained genomic surveillance of SARS-CoV-2.

3.
Front Biosci (Landmark Ed) ; 29(3): 128, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38538288

RESUMO

BACKGROUND: Chronic viral infection results in impaired immune responses rendering viral persistence. Here, we compared the quality of T-cell responses among chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-infected individuals by examining the levels of expression of selected immune activation and exhaustion molecules on circulating MAIT cells and Tfh cells. METHODS: Cytokines were measured using a commercial Bio-plex Pro Human Cytokine Grp I Panel 17-plex kit (BioRad, Hercules, CA, USA). Inflammation was assessed by measuring an array of plasma cytokines, and phenotypic alterations in CD4+ T cells including circulating Tfh cells, CD8+ T cells, and TCR iVα7.2+ MAIT cells in chronic HBV, HCV, and HIV-infected patients and healthy controls. The cells were characterized based on markers pertaining to immune activation (CD69, ICOS, and CD27) proliferation (Ki67), cytokine production (TNF-α, IFN-γ) and exhaustion (PD-1). The cytokine levels and T cell phenotypes together with cell markers were correlated with surrogate markers of disease progression. RESULTS: The activation marker CD69 was significantly increased in CD4+hi T cells, while CD8+ MAIT cells producing IFN-γ were significantly increased in chronic HBV, HCV and HIV infections. Six cell phenotypes, viz., TNF-α+CD4+lo T cells, CD69+CD8+ T cells, CD69+CD4+ MAIT cells, PD-1+CD4+hi T cells, PD-1+CD8+ T cells, and Ki67+CD4+ MAIT cells, were independently associated with decelerating the plasma viral load (PVL). TNF-α levels showed a positive correlation with increase in cytokine levels and decrease in PVL. CONCLUSION: Chronic viral infection negatively impacts the quality of peripheral MAIT cells and Tfh cells via differential expression of both activating and inhibitory receptors.


Assuntos
Infecções por HIV , Hepatite B Crônica , Hepatite C , Células T Invariantes Associadas à Mucosa , Humanos , Células T Invariantes Associadas à Mucosa/metabolismo , Receptor de Morte Celular Programada 1 , Fator de Necrose Tumoral alfa , Antígeno Ki-67 , Linfócitos T Auxiliares-Indutores/metabolismo , Citocinas/metabolismo , Vírus da Hepatite B , HIV
4.
J Med Virol ; 96(2): e29456, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38329187

RESUMO

A state-wide prospective longitudinal investigation of the genomic surveillance of the omicron B.1.1.529 SARS-CoV-2 variant and its sublineages in Tamil Nadu, India, was conducted between December 2021 and March 2023. The study aimed to elucidate their mutational patterns and their genetic interrelationship in the Indian population. The study identified several unique mutations at different time-points, which likely could attribute to the changing disease characteristics, transmission, and pathogenicity attributes of omicron variants. The study found that the omicron variant is highly competent in its mutating potentials, and that it continues to evolve in the general population, likely escaping from natural as well as vaccine-induced immune responses. Our findings suggest that continuous surveillance of viral variants at the global scenario is warranted to undertake intervention measures against potentially precarious SARS-CoV-2 variants and their evolution.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Índia/epidemiologia , Estudos Longitudinais , Estudos Prospectivos , COVID-19/epidemiologia , Genômica
5.
Lancet Reg Health Southeast Asia ; 19: 100272, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38076717

RESUMO

Background: Despite the continued vaccination efforts, there had been a surge in breakthrough infections, and the emergence of the B.1.1.529 omicron variant of SARS-CoV-2 in India. There is a paucity of information globally on the role of newer XBB variants in community transmission. Here, we investigated the mutational patterns among hospitalised patients infected with the XBB omicron sub-variant, and checked if there was any association between the rise in the number of COVID-19 cases and the observed novel mutations in Tamil Nadu, India. Methods: Nasopharyngeal and oropharyngeal swabs, collected from symptomatic and asymptomatic COVID-19 patients were subjected to real-time PCR followed by Next Generation Sequencing (NGS) to rule out the ambiguity of mutations in viruses isolated from the patients (n = 98). Using the phylogenetic association, the mutational patterns were used to corroborate clinico-demographic characteristics and disease severity among the patients. Findings: Overall, we identified 43 mutations in the S gene across 98 sequences, of which two were novel mutations (A27S and T747I) that have not been reported previously with XBB sub-variants in the available literature. Additionally, the XBB sequences from our cohort had more mutations than omicron B.1.1.529. The phylogenetic analysis comprising six major branches clearly showed convergent evolution of XBB. Our data suggests that age, and underlying conditions (e.g., diabetes, hypertension, and cardiovascular disease) or secondary complications confers increased susceptibility to infection rather than vaccination status or prior exposure. Many vaccinated individuals showed evidence of a breakthrough infection, with XBB.3 being the predominant variant identified in the study population. Interpretation: Our study indicates that the XBB variant is highly evasive from available vaccines and may be more transmissible, and potentially could emerge as the 'next' predominant variant, which likely could overwhelm the existing variants of SARS-CoV-2 omicron variants. Funding: National Health Mission (India), SIDASARC, VINNMER (Sweden), ORIP/NIH (USA).

6.
PLOS Glob Public Health ; 3(11): e0002327, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37992019

RESUMO

Early detection of latent tuberculosis infection (LTBI) is critical to TB elimination in the current WHO vision of End Tuberculosis Strategy. The study investigates whether detecting plasma cytokines could aid in diagnosing LTBI across household contacts (HHCs) positive for IGRA, HHCs negative for IGRA, and healthy controls. The plasma cytokines were measured using a commercial Bio-Plex Pro Human Cytokine 17-plex assay. Increased plasma CXCL8 and decreased MCP-1, TNF-α, and IFN-γ were associated with LTBI. Regression analysis showed that a combination of CXCL8 and MCP-1 increased the risk of LTBI among HHCs to 14-fold. Our study suggests that CXCL-8 and MCP-1 could serve as the surrogate biomarkers of LTBI, particularly in resource-limited settings. Further laboratory investigations are warranted before extrapolating CXCL8 and MCP-1 for their usefulness as surrogate biomarkers of LTBI in resource-limited settings.

7.
medRxiv ; 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37609153

RESUMO

Background: Early detection of latent tuberculosis infection (LTBI) is critical to TB elimination in the current WHO vision of End Tuberculosis Strategy. Methods: We investigated whether detecting plasma cytokines could aid in diagnosing LTBI across household contacts (HHCs) positive for IGRA, HHCs negative for IGRA, and healthy controls. We also measured the plasma cytokines using a commercial Bio-Plex Pro Human Cytokine 17-plex assay. Results: Increased plasma CXCL8 and decreased MCP-1, TNF-α, and IFN-γ were associated with LTBI. Regression analysis showed that a combination of CXCL8 and MCP-1 increased the risk of LTBI among HHCs to 14-fold. Conclusions: We postulated that CXCL8 and MCP-1 could be the surrogate biomarkers of LTBI, especially in resource-limited settings.

8.
Viral Immunol ; 36(1): 55-62, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36355180

RESUMO

Scientific observations indicate that an actively prevailing systemic condition could alleviate the pathology of another disease. Human pegivirus (HPgV), a highly ubiquitous flavivirus is believed to be associated with slow human immunodeficiency virus (HIV) disease progression, and has seldom been linked to hepatic pathology. In this study, we investigated whether HPgV seropositivity had any impact on surrogate markers of HIV disease progression in a cohort of HIV-infected HPgV seropositive (n = 28) and seronegative (n = 12) individuals who were prospectively evaluated for absolute CD4+ T cell counts, plasma viral load (PVL), liver enzymes, and plasma cytokine levels. The HIV PVL was relatively lower in HPgV seropositive than in HPgV seronegative HIV-infected subjects. Clinical markers of hepatic injury were significantly low among HPgV seropositive HIV-infected participants. HPgV seropositive individuals showed significantly higher levels of interleukin-7 (IL-7), and although not significant, the levels of IL-6 were lower among HPgV seropositive subjects. Spearman correlation analysis showed that the absolute CD4+T cell count was inversely correlated with HIV PVL. Exposure to HPgV appears to have a positive prognostic impact on the levels of surrogate biomarkers of HIV disease progression.


Assuntos
Infecções por Flaviviridae , Infecções por HIV , Humanos , Biomarcadores , Progressão da Doença , Infecções por Flaviviridae/diagnóstico , Infecções por Flaviviridae/patologia , HIV , Infecções por HIV/complicações , Pegivirus
10.
Pathog Dis ; 79(1)2021 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-33289808

RESUMO

A vast proportion of coronavirus disease 2019 (COVID-19) individuals remain asymptomatic and can shed severe acute respiratory syndrome (SARS-CoV) type 2 virus to transmit the infection, which also explains the exponential increase in the number of COVID-19 cases globally. Furthermore, the rate of recovery from clinical COVID-19 in certain pockets of the globe is surprisingly high. Based on published reports and available literature, here, we speculated a few immunovirological mechanisms as to why a vast majority of individuals remain asymptomatic similar to exotic animal (bats and pangolins) reservoirs that remain refractile to disease development despite carrying a huge load of diverse insidious viral species, and whether such evolutionary advantage would unveil therapeutic strategies against COVID-19 infection in humans. Understanding the unique mechanisms that exotic animal species employ to achieve viral control, as well as inflammatory regulation, appears to hold key clues to the development of therapeutic versatility against COVID-19.


Assuntos
COVID-19/imunologia , Síndrome da Liberação de Citocina/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Receptores KIR/imunologia , Receptores Semelhantes a Lectina de Células NK/imunologia , Zoonoses/imunologia , Animais , Animais Exóticos/virologia , Doenças Assintomáticas , COVID-19/genética , COVID-19/transmissão , COVID-19/virologia , Quirópteros/virologia , Síndrome da Liberação de Citocina/genética , Síndrome da Liberação de Citocina/prevenção & controle , Síndrome da Liberação de Citocina/virologia , Reservatórios de Doenças , Eutérios/virologia , Expressão Gênica , Especificidade de Hospedeiro , Humanos , Tolerância Imunológica , Imunidade Inata , Interferon beta/deficiência , Interferon beta/genética , Interferon beta/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/virologia , Monócitos/imunologia , Monócitos/virologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/deficiência , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Receptores KIR/deficiência , Receptores KIR/genética , Receptores Semelhantes a Lectina de Células NK/deficiência , Receptores Semelhantes a Lectina de Células NK/genética , SARS-CoV-2/patogenicidade , Fator de Necrose Tumoral alfa/deficiência , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Zoonoses/genética , Zoonoses/transmissão , Zoonoses/virologia
11.
Viral Immunol ; 33(9): 610-615, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32996843

RESUMO

Peripheral follicular helper T (pTfh) cells represent specialized CD4+ T cells that help B cells to secrete antibodies. Dengue infection appears to cause immune activation in a wide array of immune cells. Herein, we investigated the signatures of immune activation of circulating Tfh cells and mucosal-associated invariant T (MAIT) cells in adult subjects with confirmed acute clinical dengue virus (DENV) infection by multiparametric flow cytometry. The acute DENV infection induced a significant expansion of highly activated pTfh cells and circulating MAIT cells during acute febrile infection. We found a higher frequency of activated PD-1+ Tfh cells and CD38+ pTfh cells in clinical DENV infection. We also found similar activated and expanding phenotypes of MAIT cells in the patients tested. The total counts of activated pTfh cells and circulating MAIT cells were higher in dengue patients relative to healthy controls. We concluded that pTfh cells and circulating MAIT cells represent activated phenotypes in acute DENV infection.


Assuntos
Linfócitos T CD8-Positivos , Dengue/imunologia , Células T Invariantes Associadas à Mucosa , Linfócitos T Auxiliares-Indutores , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Humanos , Células T Invariantes Associadas à Mucosa/imunologia , Linfócitos T Auxiliares-Indutores/citologia , Linfócitos T Auxiliares-Indutores/imunologia
12.
J Acquir Immune Defic Syndr ; 85(1): 73-78, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32796294

RESUMO

BACKGROUND: We have previously shown an association of elevated coinhibitory molecule 2B4 expression with iNKT cells alterations in HIV disease. Herein, we show a comparative analysis of 2B4 expression on iNKT cells of HIV long-term nonprogressors (LTNPs) and progressors. METHODS: Antiretroviral therapy-naive HIV-seropositive individuals (progressors, n = 16) and LTNPs (n = 10) were recruited for this study. We used multicolor flow cytometry on frozen peripheral blood mononuclear cells to determine iNKT subset frequencies, the levels of coinhibitory 2B4 expression, and intracellular interferon-γ (IFN-γ) production. CD1d tetramer was used to characterize iNKT cells. RESULTS: We report significantly lower level of 2B4 expression on bulk LTNPs iNKT cells and on their CD4 subsets compared with HIV progressors. Furthermore, the iNKT cells from LTNPs produced higher amount of IFN-γ than HIV progressors as detected by intracellular cytokine staining. Interestingly, the frequency of 2B4iNKT cells of progressors but not LTNPs significantly correlates with CD4 T-cell count, HIV viral load, and IFN-γ production by iNKT cells. CONCLUSION: Our results suggest that in addition to suppressed HIV replication, diminished 2B4 expression and associated coinhibitory signaling, and substantial production of IFN-γ could contribute to preserved iNKT cell phenotype in LTNPs.


Assuntos
Regulação da Expressão Gênica/imunologia , Infecções por HIV/imunologia , Sobreviventes de Longo Prazo ao HIV , HIV-1 , Células T Matadoras Naturais , Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo , Regulação para Baixo , Humanos , Família de Moléculas de Sinalização da Ativação Linfocitária/genética
13.
Viral Immunol ; 33(1): 54-60, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31532346

RESUMO

Dengue virus (DENV) infection has become an increasingly common concern in tropical and subtropical regions. It has protean manifestations ranging from febrile phase to severe life-threatening illness. In this study, we estimated Th1 and Th2 cytokines and correlated the levels with dengue severity along with certain hematological and biochemical parameters. We also studied the seroprevalence of dengue between October and December 2017 at the Government Theni Medical College, India. Individuals with dengue fever (DF) were positive for either IgM or IgG, or both. The biochemical and hematological parameters along with plasma tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), granulocyte monocyte-colony stimulating factor (GM-CSF), interleukin (IL)-13, IL-12p70, IL-10, IL-5, IL-4, and IL-2 cytokines were estimated. The prevalence of DF was 42.9% during the study period. IL-2, TNF-α, IL-4, and IL-10 levels were significantly elevated (p < 0.005) in patients with secondary DENV infection, whereas the level of IL-13 remained unaltered during both primary and secondary infections. No statistically significant difference was noticed with IL-12p70, IL-5, IFN-γ, and GM-CSF between the healthy controls and the primary and secondary DENV-infected groups. Increase of 1 unit of TNF-α was associated with a decrease of 160 units of blood platelets. Together, the study suggests that TNF-α could play a key role in the pathogenesis of dengue, and despite the decrease in platelet levels, it remains to be seen whether any other inflammatory cells regulate the levels of TNF-α in DENV infection.


Assuntos
Plaquetas/citologia , Citocinas/imunologia , Dengue/sangue , Dengue/imunologia , Fator de Necrose Tumoral alfa/sangue , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Citocinas/sangue , Dengue/epidemiologia , Feminino , Humanos , Índia/epidemiologia , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Células Th1/imunologia , Células Th2/imunologia , Adulto Jovem
14.
Front Microbiol ; 10: 2789, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31921004

RESUMO

Tuberculosis (TB) treatment monitoring is paramount to clinical decision-making and the host biomarkers appears to play a significant role. The currently available diagnostic technology for TB detection is inadequate. Although GeneXpert detects total DNA present in the sample regardless live or dead bacilli present in clinical samples, all the commercial tests available thus far have low sensitivity. Humoral responses against Mycobacterium tuberculosis (Mtb) antigens are generally low, which precludes the use of serological tests for TB diagnosis, prognosis, and treatment monitoring. Mtb-specific CD4+ T cells correlate with Mtb antigen/bacilli burden and hence might serve as good biomarkers for monitoring treatment progress. Omics-based techniques are capable of providing a more holistic picture for disease mechanisms and are more accurate in predicting TB disease outcomes. The current review aims to discuss some of the recent advances on TB biomarkers, particularly host biomarkers that have the potential to diagnose and differentiate active TB and LTBI as well as their use in disease prognosis and treatment monitoring.

15.
Cells ; 7(10)2018 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-30322028

RESUMO

Hepatitis C virus (HCV) represents a challenging global health threat to ~200 million infected individuals. Clinical data suggest that only ~10⁻15% of acutely HCV-infected individuals will achieve spontaneous viral clearance despite exuberant virus-specific immune responses, which is largely attributed to difficulties in recognizing the pathognomonic symptoms during the initial stages of exposure to the virus. Given the paucity of a suitable small animal model, it is also equally challenging to study the early phases of viral establishment. Further, the host factors contributing to HCV chronicity in a vast majority of acutely HCV-infected individuals largely remain unexplored. The last few years have witnessed a surge in studies showing that HCV adopts myriad mechanisms to disconcert virus-specific immune responses in the host to establish persistence, which includes, but is not limited to viral escape mutations, viral growth at privileged sites, and antagonism. Here we discuss a few hitherto poorly explained mechanisms employed by HCV that are believed to lead to chronicity in infected individuals. A better understanding of these mechanisms would aid the design of improved therapeutic targets against viral establishment in susceptible individuals.

16.
Front Immunol ; 9: 472, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29616020

RESUMO

Mucosal-associated invariant T (MAIT) cells, defined as CD161++TCR iVα7.2+ T cells, play an important role in the innate defense against bacterial infections, and their functionality is impaired in chronic viral infections. Here, we investigated the frequency and functional role of MAIT cells in chronic hepatitis B virus (HBV) infection. The peripheral CD3+CD161++TCR iVα7.2+ MAIT cells in chronic HBV-infected patients and healthy controls were phenotypically characterized based on CD57, PD-1, TIM-3, and CTLA-4, as well as HLA-DR and CD38 expression. The frequency of MAIT cells was significantly decreased among chronic HBV-infected individuals as compared to controls. Expression of CD57, PD-1, CTLA-4, as well as HLA-DR and CD38 on MAIT cells was significantly elevated in chronic HBV-infected individuals relative to controls. The percentage of T cell receptor (TCR) iVα7.2+ CD161+ MAIT cells did not correlate with HBV viral load but inversely with HLA-DR on CD4+ T cells and MAIT cells and with CD57 on CD8+ T cells suggesting that decrease of MAIT cells may not be attributed to direct infection by HBV but driven by HBV-induced chronic immune activation. The percentage and expression levels of PD-1 as well as CTLA-4 on MAIT cells inversely correlated with plasma HBV-DNA levels, which may suggest either a role for MAIT cells in the control of HBV infection or the effect of HBV replication in the liver on MAIT cell phenotype. We report that decrease of TCR iVα7.2+ MAIT cells in the peripheral blood and their functions were seemingly impaired in chronic HBV-infected patients likely because of the increased expression of PD-1.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Regulação da Expressão Gênica/imunologia , Hepatite B Crônica/imunologia , Subfamília B de Receptores Semelhantes a Lectina de Células NK/imunologia , Receptor de Morte Celular Programada 1/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Adulto , Linfócitos T CD8-Positivos/patologia , DNA Viral/imunologia , Feminino , Hepatite B Crônica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa/imunologia , Mucosa/patologia
17.
Medicine (Baltimore) ; 97(5): e9713, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29384851

RESUMO

Dengue virus is one of the most widespread flaviviruses that re-emerged throughout recent decades. The progression from mild dengue to severe dengue (SD) with the complications such as vascular leakage and hemorrhage increases the fatality rate of dengue. The pathophysiology of SD is not entirely clear. To investigate potential biomarkers that are suggestive of pathogenesis of SD, a small panel of serum samples selected from 1 healthy individual, 2 dengue patients without warning signs (DWS-), 2 dengue patients with warning signs (DWS+), and 5 patients with SD were subjected to a pilot analysis using Sengenics Immunome protein array. The overall fold changes of protein expressions and clustering heat map revealed that PFKFB4, TPM1, PDCL3, and PTPN20A were elevated among patients with SD. Differential expression analysis identified that 29 proteins were differentially elevated greater than 2-fold in SD groups than DWS- and DWS+. From the 29 candidate proteins, pathways enrichment analysis also identified insulin signaling and cytoskeleton pathways were involved in SD, suggesting that the insulin pathway may play a pivotal role in the pathogenesis of SD.


Assuntos
Biomarcadores/sangue , Dengue/sangue , Dengue/imunologia , Humanos , Projetos Piloto , Análise Serial de Proteínas , Índice de Gravidade de Doença
18.
Innate Immun ; 23(5): 459-467, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28606013

RESUMO

Hepatitis B virus (HBV) infection is a major cause of chronic liver disease that may progress to liver cirrhosis and hepatocellular carcinoma. Host immune responses represent the key determinants of HBV clearance or persistence. Here, we investigated the role of the early activation marker, CD69 and effector cytokines, granzyme B (GrB) and IFN-γ in the exhaustion of innate-like TCR Vα7.2+CD4+T cells, in 15 individuals with chronic HBV (CHB) infection where six were HBV DNA+ and nine were HBV DNA-. The percentage of cytokine-producing T cells and MAIT cells were significantly perturbed in HBV patients relative to healthy controls (HCs). The intracellular expression of GrB and IFN-γ was significantly reduced in MAIT cells derived from HBV-infected patients as compared to HCs, and the levels correlated with the percentage and levels [mean fluorescence intensity (MFI)] of CD69 expression. The total expression of CD69 (iMFI) was lower in CHB patients as compared to HCs. The frequency of CD69+ cells correlated with the levels of cytokine expression (MFI), particularly in CHB patients as compared to HCs. In summary, the polyfunctionality of peripheral T cells was significantly reduced among CHB patients, especially in the TCR Vα7.2+CD4+T cells, and the levels of cytokine expression correlated with functional cytokine levels.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Linfócitos T CD4-Positivos/imunologia , Carcinoma Hepatocelular/imunologia , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/imunologia , Lectinas Tipo C/metabolismo , Neoplasias Hepáticas/imunologia , Células T Invariantes Associadas à Mucosa/imunologia , Adulto , Células Cultivadas , Citotoxicidade Imunológica , Feminino , Granzimas/metabolismo , Humanos , Imunidade Inata , Interferon gama/metabolismo , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Carga Viral
19.
J Transl Med ; 15(1): 121, 2017 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-28569153

RESUMO

BACKGROUND: Currently, several assays can diagnose acute dengue infection. However, none of these assays can predict the severity of the disease. Biomarkers that predicts the likelihood that a dengue patient will develop a severe form of the disease could permit more efficient patient triage and allows better supportive care for the individual in need, especially during dengue outbreaks. METHODS: We measured 20 plasma markers i.e. IFN-γ, IL-10, granzyme-B, CX3CL1, IP-10, RANTES, CXCL8, CXCL6, VCAM, ICAM, VEGF, HGF, sCD25, IL-18, LBP, sCD14, sCD163, MIF, MCP-1 and MIP-1ß in 141 dengue patients in over 230 specimens and correlate the levels of these plasma markers with the development of dengue without warning signs (DWS-), dengue with warning signs (DWS+) and severe dengue (SD). RESULTS: Our results show that the elevation of plasma levels of IL-18 at both febrile and defervescence phase was significantly associated with DWS+ and SD; whilst increase of sCD14 and LBP at febrile phase were associated with severity of dengue disease. By using receiver operating characteristic (ROC) analysis, the IL-18, LBP and sCD14 were significantly predicted the development of more severe form of dengue disease (DWS+/SD) (AUC = 0.768, P < 0.0001; AUC = 0.819, P < 0.0001 and AUC = 0.647, P = 0.014 respectively). Furthermore, we also found that the levels of VEGF were directly correlated and sCD14 was inversely correlated with platelet count, suggesting that the endothelial activation and microbial translocation may played a role in pathogenesis of dengue disease. CONCLUSIONS: Given that the elevation IL-18, LBP and sCD14 among patients with severe form of dengue disease, our findings suggest a pathogenic role for an aberrant inflammasome and monocyte activation in the development of severe form of dengue disease.


Assuntos
Dengue/sangue , Dengue/imunologia , Monócitos/citologia , Dengue Grave/sangue , Dengue Grave/imunologia , Proteínas de Fase Aguda , Adulto , Área Sob a Curva , Biomarcadores/sangue , Proteínas de Transporte/sangue , Citocinas/metabolismo , Dengue/diagnóstico , Vírus da Dengue , Surtos de Doenças , Feminino , Humanos , Inflamassomos , Inflamação , Interleucina-18/sangue , Receptores de Lipopolissacarídeos/sangue , Estudos Longitudinais , Masculino , Glicoproteínas de Membrana/sangue , Contagem de Plaquetas , Curva ROC , Dengue Grave/diagnóstico , Adulto Jovem
20.
Front Immunol ; 8: 338, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28396665

RESUMO

The CD1d-restricted invariant natural killer T (iNKT) cells are implicated in innate immune responses against human immunodeficiency virus (HIV). However, the determinants of cellular dysfunction across the iNKT cells subsets are seldom defined in HIV disease. Herein, we provide evidence for the involvement of the negative checkpoint regulator (NCR) 2B4 in iNKT cell alteration in a well-defined cohort of HIV-seropositive anti-retroviral therapy (ART) naïve, ART-treated, and elite controllers (ECs). We report on exaggerated 2B4 expression on iNKT cells of HIV-infected treatment-naïve individuals. In sharp contrast to CD4-iNKT cells, 2B4 expression was significantly higher on CD4+ iNKT cell subset. Notably, an increased level of 2B4 on iNKT cells was strongly correlated with parameters associated with HIV disease progression. Further, iNKT cells from ART-naïve individuals were defective in their ability to produce intracellular IFN-γ. Together, our results suggest that the levels of 2B4 expression and the downstream co-inhibitory signaling events may contribute to impaired iNKT cell responses.

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