共查询到20条相似文献,搜索用时 12 毫秒
1.
Amelia R. Hofstetter Juan A. De La Cruz Weiping Cao Jenish Patel Jessica A. Belser James McCoy Justine S. Liepkalns Samuel Amoah Guangjie Cheng Priya Ranjan Becky A. Diebold Wun-Ju Shieh Sherif Zaki Jacqueline M. Katz Suryaprakash Sambhara J. David Lambeth Shivaprakash Gangappa 《PloS one》2016,11(2)
The role of the reactive oxygen species-producing NADPH oxidase family of enzymes in the pathology of influenza A virus infection remains enigmatic. Previous reports implicated NADPH oxidase 2 in influenza A virus-induced inflammation. In contrast, NADPH oxidase 1 (Nox1) was reported to decrease inflammation in mice within 7 days post-influenza A virus infection. However, the effect of NADPH oxidase 1 on lethality and adaptive immunity after influenza A virus challenge has not been explored. Here we report improved survival and decreased morbidity in mice with catalytically inactive NADPH oxidase 1 (Nox1*/Y) compared with controls after challenge with A/PR/8/34 influenza A virus. While changes in lung inflammation were not obvious between Nox1*/Y and control mice, we observed alterations in the T cell response to influenza A virus by day 15 post-infection, including increased interleukin-7 receptor-expressing virus-specific CD8+ T cells in lungs and draining lymph nodes of Nox1*/Y, and increased cytokine-producing T cells in lungs and spleen. Furthermore, a greater percentage of conventional and interstitial dendritic cells from Nox1*/Y draining lymph nodes expressed the co-stimulatory ligand CD40 within 6 days post-infection. Results indicate that NADPH oxidase 1 modulates the innate and adaptive cellular immune response to influenza virus infection, while also playing a role in host survival. Results suggest that NADPH oxidase 1 inhibitors may be beneficial as adjunct therapeutics during acute influenza infection. 相似文献
2.
LaTonya D. Williams Nilesh Amatya Anju Bansal Steffanie Sabbaj Sonya L. Heath Irini Sereti Paul A. Goepfert 《Journal of virology》2014,88(17):10259-10263
Interleukin-21 (IL-21) can be produced by CD8 T cells from HIV-1-infected individuals and those with autoimmune disease, but the mechanism remains poorly understood. Here we demonstrate that IL-21-producing CD8 T cells are not associated with CD4 depletion and are absent in patients with idiopathic CD4 lymphocytopenia. Instead, IL-21 production by CD8 T cells was associated with high levels of activation, suggesting that these cells emerge as a consequence of excessive chronic immune activation rather than CD4 lymphopenia. 相似文献
3.
Catherine M. Card W. John Rutherford Suzie Ramdahin Xiaojian Yao Makobu Kimani Charles Wachihi Joshua Kimani Francis A. Plummer T. Blake Ball Keith R. Fowke 《PloS one》2012,7(9)
Background
HIV preferentially establishes productive infection in activated CD4+ T cells. Since proportions of activated CD4+ T cells vary between individuals, this study aimed to determine if individuals with a greater proportion of activated CD4+ T cells would be more susceptible to in vitro HIV infection.Methodology/Principal Findings
Unstimulated peripheral blood mononuclear cells (PBMC) from various donors were inoculated with HIVML1956 in vitro. HIV replication was evaluated by HIV p24 ELISA of culture supernatants and intracellular staining for HIV p24, which was detected by flow cytometry. Baseline T cell phenotypes and infected cell phenotypes were also evaluated by flow cytometry. Ex vivo phenotyping at the time of blood draw showed that elevated T cell activation and reduced Tregs were associated with increased cellular susceptibility to in vitro infection. Furthermore, the infected CD4+ T cell population was enriched for activated cells.Conclusion/Significance
These data suggest that CD4+ T cell quiescence provides an environment less conducive to the establishment of HIV infection by limiting the pool of activated target cells. 相似文献4.
5.
Nadia Wauquier Pierre Becquart Cindy Padilla Sylvain Baize Eric M. Leroy 《PLoS neglected tropical diseases》2010,4(10)
Background
Ebolavirus species Zaire (ZEBOV) causes highly lethal hemorrhagic fever, resulting in the death of 90% of patients within days. Most information on immune responses to ZEBOV comes from in vitro studies and animal models. The paucity of data on human immune responses to this virus is mainly due to the fact that most outbreaks occur in remote areas. Published studies in this setting, based on small numbers of samples and limited panels of immunological markers, have given somewhat different results.Methodology/Principal Findings
Here, we studied a unique collection of 56 blood samples from 42 nonsurvivors and 14 survivors, obtained during the five outbreaks that occurred between 1996 and 2003 in Gabon and Republic of Congo. Using Luminex technology, we assayed 50 cytokines in all 56 samples and performed phenotypic analyses by flow cytometry. We found that fatal outcome was associated with hypersecretion of numerous proinflammatory cytokines (IL-1β, IL-1RA, IL-6, IL-8, IL-15 and IL-16), chemokines and growth factors (MIP-1α, MIP-1β, MCP-1, M-CSF, MIF, IP-10, GRO-α and eotaxin). Interestingly, no increase of IFNα2 was detected in patients. Furthermore, nonsurvivors were also characterized by very low levels of circulating cytokines produced by T lymphocytes (IL-2, IL-3, IL-4, IL-5, IL-9, IL-13) and by a significant drop of CD3+CD4+ and CD3+CD8+ peripheral cells as well as a high increase in CD95 expression on T lymphocytes.Conclusions/Significance
This work, the largest study to be conducted to date in humans, showed that fatal outcome is associated with aberrant innate immune responses and with global suppression of adaptive immunity. The innate immune reaction was characterized by a “cytokine storm,” with hypersecretion of numerous proinflammatory cytokines, chemokines and growth factors, and by the noteworthy absence of antiviral IFNα2. Immunosuppression was characterized by very low levels of circulating cytokines produced by T lymphocytes and by massive loss of peripheral CD4 and CD8 lymphocytes, probably through Fas/FasL-mediated apoptosis. 相似文献6.
Hinta Meijerink Agnes Indrati Fitri Utami Suharyani Soedarmo Bachti Alisjahbana Mihai G. Netea Reinout van Crevel Rudi Wisaksana Andre Jam van der Ven 《PloS one》2015,10(4)
Background
Opioid use is associated with increased incidence of infectious diseases. Although experimental studies have shown that opioids affect various functions of immune cells, only limited data are available from human studies. Drug use is an important risk factor for HIV transmission; however no data are available whether heroin and/or methadone modulate immune response. Therefore, we examined the effect of heroin and methadone use among HIV-infected individuals on the production of cytokines after ex vivo stimulation with various pathogens.Methods
Treatment naïve HIV-infected individuals from Indonesia were recruited. Several cohorts of individuals were recruited: 1) using heroin 2) receiving methadone opioid substitution 3) using heroin over 1 year ago and 4) controls (never used opioids). Whole blood was stimulated with Mycobacterium tuberculosis, Candida albicans and LPS for 24 to 48 hours. Cytokine production (IL-1 β, IL-6, IL-10, IFN-α, IFN-γ and TNF-α) was determined using multiplex beads assay.Results
Among 82 individuals, the cytokine levels in unstimulated samples did not differ between groups. Overall, heroin users had significantly lower cytokine response after exposure to LPS (p<0.05). After stimulation with either M. tuberculosis or C. albicans the cytokine production of all groups were comparable.Conclusion
The cytokine production after exposure to LPS is significantly down-regulated in HIV-infected heroin users. Interesting, methadone use did not suppress cytokine response, which could have implications guidelines of opioid substitution. 相似文献7.
The eusocial honey bee, Apis mellifera, has evolved remarkable abilities to survive extreme seasonal differences in temperature and availability of resources by dividing the worker caste into two groups that differ in physiology and lifespan: summer and winter bees. Most of the recent major losses of managed honey bee colonies occur during the winter, suggesting that winter bees may have compromised immune function and higher susceptibility to diseases. We tested this hypothesis by comparing the expression of eight immune genes and naturally occurring infection levels of deformed wing virus (DWV), one of the most widespread viruses in A. mellifera populations, between summer and winter bees. Possible interactions between immune response and physiological activity were tested by measuring the expression of vitellogenin and methyl farnesoate epoxidase, a gene coding for the last enzyme involved in juvenile hormone biosynthesis. Our data show that high DWV loads in winter bees correlate with reduced expression of genes involved in the cellular immune response and physiological activity and high expression of humoral immune genes involved in antibacterial defense compared with summer bees. This expression pattern could reflect evolutionary adaptations to resist bacterial pathogens and economize energy during the winter under a pathogen landscape with reduced risk of pathogenic viral infections. The outbreak of Varroa destructor infestation could have overcome these adaptations by promoting the transmission of viruses. Our results suggest that reduced cellular immune function during the winter may have increased honey bee’s susceptibility to DWV. These results contribute to our understanding of honey bee colony losses in temperate regions. 相似文献
8.
Nichole R. Klatt Steven E. Bosinger Melicent Peck Laura E. Richert-Spuhler Anke Heigele Jillian P. Gile Nirav Patel Jessica Taaffe Boris Julg David Camerini Carlo Torti Jeffrey N. Martin Steven G. Deeks Elizabeth Sinclair Frederick M. Hecht Michael M. Lederman Mirko Paiardini Frank Kirchhoff Jason M. Brenchley Peter W. Hunt Guido Silvestri 《PLoS pathogens》2014,10(8)
A rare subset of HIV-infected individuals, designated viremic non-progressors (VNP), remain asymptomatic and maintain normal levels of CD4+ T-cells despite persistently high viremia. To identify mechanisms potentially responsible for the VNP phenotype, we compared VNPs (average >9 years of HIV infection) to HIV-infected individuals who have similar CD4+ T-cell counts and viral load, but who are likely to progress if left untreated (“putative progressors”, PP), thus avoiding the confounding effect of differences related to substantial CD4+ T cell depletion. We found that VNPs, compared to PPs, had preserved levels of CD4+ stem cell memory cells (TSCM (p<0.0001), which was associated with decreased HIV infection of these cells in VNPs (r = −0.649, p = 0.019). In addition, VNPs had decreased HIV infection in CD4+ central memory (TCM) cells (p = 0.035), and the total number of TCM cells was associated with increased proliferation of memory CD4+ T cells (r = 0.733, p = 0.01). Our results suggest that, in HIV-infected VNPs, decreased infection of CD4+ TCM and TSCM, cells are involved in preservation of CD4+ T cell homeostasis and lack of disease progression despite high viremia. 相似文献
9.
Sergio Serrano-Villar Talia Sainz Sulggi A. Lee Peter W. Hunt Elizabeth Sinclair Barbara L. Shacklett April L. Ferre Timothy L. Hayes Ma Somsouk Priscilla Y. Hsue Mark L. Van Natta Curtis L. Meinert Michael M. Lederman Hiroyu Hatano Vivek Jain Yong Huang Frederick M. Hecht Jeffrey N. Martin Joseph M. McCune Santiago Moreno Steven G. Deeks 《PLoS pathogens》2014,10(5)
A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART) fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined. Using data from four distinct clinical cohorts and three clinical trials, we show that a low CD4/CD8 ratio in HIV-infected adults during otherwise effective ART (after CD4 count recovery above 500 cells/mm3) is associated with a number of immunological abnormalities, including a skewed T cell phenotype from naïve toward terminally differentiated CD8+ T cells, higher levels of CD8+ T cell activation (HLADR+CD38+) and senescence (CD28− and CD57+CD28−), and higher kynurenine/tryptophan ratio. Changes in the peripheral CD4/CD8 ratio are also reflective of changes in gut mucosa, but not in lymph nodes. In a longitudinal study, individuals who initiated ART within six months of infection had greater CD4/CD8 ratio increase compared to later initiators (>2 years). After controlling for age, gender, ART duration, nadir and CD4 count, the CD4/CD8 ratio predicted increased risk of morbidity and mortality. Hence, a persistently low CD4/CD8 ratio during otherwise effective ART is associated with increased innate and adaptive immune activation, an immunosenescent phenotype, and higher risk of morbidity/mortality. This ratio may prove useful in monitoring response to ART and could identify a unique subset of individuals needed of novel therapeutic interventions. 相似文献
10.
Mark H. Kuniholm Christina M. Parrinello Kathryn Anastos Michael Augenbraun Michael Plankey Marek Nowicki Marion Peters Elizabeth T. Golub Nell Lurain Alan L. Landay Howard D. Strickler Robert C. Kaplan 《PloS one》2013,8(4)
Background
Individuals with HIV infection exhibit high cytomegalovirus (CMV) IgG levels, but there are few data regarding the association of hepatitis C virus (HCV) with the immune response against CMV.Methods
Associations of HCV with CMV seropositivity and CMV IgG levels were studied in 635 HIV-infected women, 187 of whom were HCV-seropositive, with adjustment in multivariable models for age, race/ethnicity, and HIV disease characteristics. Eighty one percent of the women reported receipt of highly active antiretroviral therapy (HAART) prior to or at CMV testing.Results
In adjusted models women with chronic HCV had higher CMV IgG levels than those without HCV RNA (β = 2.86, 95% CI:0.89 – 4.83; P = 0.004). The association of HCV RNA with CMV IgG differed by age (P interaction = 0.0007), with a strong association observed among women in the low and middle age tertiles (≤45.3 years of age; β = 6.21, 95% CI:3.30 – 9.11, P<0.0001) but not among women in the high age tertile. CMV IgG levels were not associated with non-invasive measures of liver disease, APRI and FIB-4, or with HCV RNA level and adjustment for Epstein-Barr virus (EBV) IgG levels did not affect the association between HCV and CMV.Conclusions
CMV IgG levels are higher in HCV/HIV co-infected women than in HIV mono-infected women. Further research on the association of HCV with CMV IgG is indicated because prior studies have found CMV IgG to be associated with morbidity and mortality in the general population and subclinical carotid artery disease in HIV-infected patients. 相似文献11.
Sarah Patterson Patricia Moran Elissa Epel Elizabeth Sinclair Margaret E. Kemeny Steven G. Deeks Peter Bacchetti Michael Acree Lorrie Epling Clemens Kirschbaum Frederick M. Hecht 《PloS one》2013,8(7)
Objective
The level of T cell activation in untreated HIV disease is strongly and independently associated with risk of immunologic and clinical progression. The factors that influence the level of activation, however, are not fully defined. Since endogenous glucocorticoids are important in regulating inflammation, we sought to determine whether less optimal diurnal cortisol patterns are associated with greater T cell activation.Methods
We studied 128 HIV-infected adults who were not on treatment and had a CD4+ T cell count above 250 cells/µl. We assessed T cell activation by CD38 expression using flow cytometry, and diurnal cortisol was assessed with salivary measurements.Results
Lower waking cortisol levels correlated with greater T cell immune activation, measured by CD38 mean fluorescent intensity, on CD4+ T cells (r = −0.26, p = 0.006). Participants with lower waking cortisol also showed a trend toward greater activation on CD8+ T cells (r = −0.17, p = 0.08). A greater diurnal decline in cortisol, usually considered a healthy pattern, correlated with less CD4+ (r = 0.24, p = 0.018) and CD8+ (r = 0.24, p = 0.017) activation.Conclusions
These data suggest that the hypothalamic-pituitary-adrenal (HPA) axis contributes to the regulation of T cell activation in HIV. This may represent an important pathway through which psychological states and the HPA axis influence progression of HIV. 相似文献12.
Diseases caused by dengue virus (DV) infection vary in severity, with symptoms ranging from mild fever to life threatening dengue hemorrhage fever (DHF) and dengue shock syndrome (DSS). Clinical studies have shown that significant decrease in the level of lipoproteins is correlated with severe illness in DHF/DSS patients. Available evidence also indicates that lipoproteins including high-density lipoprotein (HDL) and low-density lipoprotein (LDL) are able to facilitate cell entry of HCV or other flaviviruses via corresponding lipoprotein receptors. In this study, we found that pre-incubation of DV with human serum leads to an enhanced DV infectivity in various types of cells. Such enhancement could be due to interactions between serum components and DV particles. Through co-immunoprecipitation we revealed that apolipoprotein A-I (ApoA-I), the major protein component in HDL, is associated with DV particles and is able to promote DV infection. Based on that observation, we further found that siRNA knockdown of the scavenger receptor class B type I (SR-BI), the cell receptor of ApoA-I, abolished the activity of ApoA-I in enhancement of DV infection. This suggests that ApoA-I bridges DV particles and cell receptor SR-BI and facilitates entry of DV into cells. FACS analysis of cell surface dengue antigen after virus absorption further confirmed that ApoA-I enhances DV infection via promoting initial attachment of the virus to cells. These findings illustrate a novel entry route of DV into cells, which may provide insights into the functional importance of lipoproteins in dengue pathogenesis. 相似文献
13.
Andréia Manso de Matos Karina Inacio Carvalho Daniela Santoro Rosa Lucy Santos Villas-Boas Wanessa Cardoso da Silva Célia Luiza de Lima Rodrigues Olímpia Massae Nakasone Peel Furtado Oliveira José Eduardo Levi Evaldo Stanislau Affonso Araújo Claudio Sergio Pannuti Expedito José Albuquerque Luna Esper George Kallas 《PLoS neglected tropical diseases》2015,9(2)
Dengue fever induces a robust immune response, including massive T cell activation. The level of T cell activation may, however, be associated with more severe disease. In this study, we explored the level of CD8+ T lymphocyte activation in the first six days after onset of symptoms during a DENV2 outbreak in early 2010 on the coast of São Paulo State, Brazil. Using flow cytometry we detected a progressive increase in the percentage of CD8+ T cells in 74 dengue fever cases. Peripheral blood mononuclear cells from 30 cases were thawed and evaluated using expanded phenotyping. The expansion of the CD8+ T cells was coupled with increased Ki67 expression. Cell activation was observed later in the course of disease, as determined by the expression of the activation markers CD38 and HLA-DR. This increased CD8+ T lymphocyte activation was observed in all memory subsets, but was more pronounced in the effector memory subset, as defined by higher CD38 expression. Our results show that most CD8+ T cell subsets are expanded during DENV2 infection and that the effector memory subset is the predominantly affected sub population. 相似文献
14.
Mar Masiá Catalina Robledano Victoria Ortiz de la Tabla Pedro Antequera Blanca Lumbreras Ildefonso Hernández Félix Gutiérrez 《PloS one》2014,9(8)
Objectives
Infection with co-pathogens is one of the postulated factors contributing to persistent inflammation and non-AIDS events in virologically-suppressed HIV-infected patients. We aimed to investigate the relationship of human herpesvirus-8 (HHV-8), a vasculotropic virus implicated in the pathogenesis of Kaposi''s sarcoma, with inflammation and subclinical atherosclerosis in HIV-infected patients.Methods
Prospective study including virologically suppressed HIV-infected patients. Several blood biomarkers (highly-sensitive C-reactive protein [hsCRP], tumour necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1, vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, malondialdehyde, plasminogen activator inhibitor [PAI-1], D-dimer, sCD14, sCD163, CD4/CD38/HLA-DR, and CD8/CD38/HLA-DR), serological tests for HHV-8 and the majority of herpesviruses, carotid intima-media thickness, and endothelial function through flow-mediated dilatation of the brachial artery were measured.Results
A total of 136 patients were included, 34.6% of them infected with HHV-8. HHV-8-infected patients were more frequently co-infected with herpes simplex virus type 2 (HSV-2) (P<0.001), and less frequently with hepatitis C virus (HCV) (P = 0.045), and tended to be older (P = 0.086). HHV-8-infected patients had higher levels of hsCRP (median [interquartile range], 3.63 [1.32–7.54] vs 2.08 [0.89–4.11] mg/L, P = 0.009), CD4/CD38/HLA-DR (7.67% [4.10–11.86]% vs 3.86% [2.51–7.42]%, P = 0.035) and CD8/CD38/HLA-DR (8.02% [4.98–14.09]% vs 5.02% [3.66–6.96]%, P = 0.018). After adjustment for the traditional cardiovascular risk factors, HCV and HSV-2 infection, the associations remained significant: adjusted difference between HHV-8 positive and negative patients (95% confidence interval) for hsCRP, 74.19% (16.65–160.13)%; for CD4/CD38/HLA-DR, 89.65% (14.34–214.87)%; and for CD8/CD38/HLA-DR, 58.41% (12.30–123.22)%. Flow-mediated dilatation and total carotid intima-media thickness were not different according to HHV-8 serostatus.Conclusion
In virologically suppressed HIV-infected patients, coinfection with HHV-8 is associated with increased inflammation and immune activation. This might contribute to increase the risk of non-AIDS events, including accelerated atherosclerotic disease. 相似文献15.
16.
Vesselin T. Tomov Lisa C. Osborne Douglas V. Dolfi Gregory F. Sonnenberg Laurel A. Monticelli Kathleen Mansfield Herbert W. Virgin David Artis E. John Wherry 《Journal of virology》2013,87(12):7015-7031
Norovirus (NV) gastroenteritis is a major contributor to global morbidity and mortality, yet little is known about immune mechanisms leading to NV control. Previous studies using the murine norovirus (MNV) model have established a key role for T cells in MNV clearance. Despite these advances, important questions remain regarding the magnitude, location, and dynamics of the MNV-specific T cell response. To address these questions, we identified MNV-specific major histocompatibility complex (MHC) class I immunodominant epitopes using an overlapping peptide screen. One of these epitopes (amino acids 519 to 527 of open reading frame 2 [ORF2519-527]) was highly conserved among all NV genogroups. Using MHC class I peptide tetramers, we tracked MNV-specific CD8 T cells in lymphoid and mucosal sites during infection with two MNV strains with distinct biological behaviors, the acutely cleared strain CW3 and the persistent strain CR6. Here, we show that enteric MNV infection elicited robust T cell responses primarily in the intestinal mucosa and that MNV-specific CD8 T cells dynamically regulated the expression of surface molecules associated with activation, differentiation, and homing. Furthermore, compared to MNV-CW3 infection, chronic infection with MNV-CR6 resulted in fewer and less-functional CD8 T cells, and this difference was evident as early as day 8 postinfection. Finally, MNV-specific CD8 T cells were capable of reducing the viral load in persistently infected Rag1−/− mice, suggesting that these cells are a crucial component of NV immunity. Collectively, these data provide fundamental new insights into the adaptive immune response to two closely related NV strains with distinct biological behaviors and bring us closer to understanding the correlates of protective antiviral immunity in the intestine. 相似文献
17.
Verónica Martín Elena Pascual Miguel Avia Lourdes Pe?a Félix Valcárcel Noemí Sevilla 《PloS one》2015,10(11)
Bluetongue virus (BTV) is an economically important Orbivirus of the Reoviridae family that causes a hemorrhagic disease in ruminants. Its control has been achieved by inactivated-vaccines that have proven to protect against homologous BTV challenge although unable to induce long-term immunity. Therefore, a more efficient control strategy needs to be developed. Recombinant adenovirus vectors are lead vaccine candidates for protection of several diseases, mainly because of their potency to induce potent T cell immunity. Here we report the induction of humoral and T-cell mediated responses able to protect animals against BTV challenge by recombinant replication-defective human adenovirus serotype 5 (Ad5) expressing either VP7, VP2 or NS3 BTV proteins. First we used the IFNAR(-/-) mouse model system to establish a proof of principle, and afterwards we assayed the protective efficacy in sheep, the natural host of BTV. Mice were completely protected against BTV challenge, developing humoral and BTV-specific CD8+- and CD4+-T cell responses by vaccination with the different rAd5. Sheep vaccinated with Ad5-BTV-VP2 and Ad5-BTV-VP7 or only with Ad5-BTV-VP7 and challenged with BTV showed mild disease symptoms and reduced viremia. This partial protection was achieved in the absence of neutralizing antibodies but strong BTV-specific CD8+ T cell responses in those sheep vaccinated with Ad5-BTV-VP7. These data indicate that rAd5 is a suitable vaccine vector to induce T cell immunity during BTV vaccination and provide new data regarding the relevance of T cell responses in protection during BTV infection. 相似文献
18.
Cornelia A. M. van de Weg Ralph M. H. G. Huits Cláudio S. Pannuti Rosalba M. Brouns Riemsdijk W. A. van den Berg Henk-Jan van den Ham Byron E. E. Martina Albert D. M. E. Osterhaus Mihai G. Netea Joost C. M. Meijers Eric C. M. van Gorp Esper G. Kallas 《PLoS neglected tropical diseases》2014,8(10)
Background
During a dengue outbreak on the Caribbean island Aruba, highly elevated levels of ferritin were detected in dengue virus infected patients. Ferritin is an acute-phase reactant and hyperferritinaemia is a hallmark of diseases caused by extensive immune activation, such as haemophagocytic lymphohistiocytosis. The aim of this study was to investigate whether hyperferritinaemia in dengue patients was associated with clinical markers of extensive immune activation and coagulation disturbances.Methodology/Principal Findings
Levels of ferritin, standard laboratory markers, sIL-2R, IL-18 and coagulation and fibrinolytic markers were determined in samples from patients with uncomplicated dengue in Aruba. Levels of ferritin were significantly increased in dengue patients compared to patients with other febrile illnesses. Moreover, levels of ferritin associated significantly with the occurrence of viraemia. Hyperferritinaemia was also significantly associated with thrombocytopenia, elevated liver enzymes and coagulation disturbances. The results were validated in a cohort of dengue virus infected patients in Brazil. In this cohort levels of ferritin and cytokine profiles were determined. Increased levels of ferritin in dengue virus infected patients in Brazil were associated with disease severity and a pro-inflammatory cytokine profile.Conclusions/Significance
Altogether, we provide evidence that ferritin can be used as a clinical marker to discriminate between dengue and other febrile illnesses. The occurrence of hyperferritinaemia in dengue virus infected patients is indicative for highly active disease resulting in immune activation and coagulation disturbances. Therefore, we recommend that patients with hyperferritinaemia are monitored carefully. 相似文献19.
Human immunodeficiency virus type 1 (HIV-1) infects and destroys cells of the immune system leading to an overt immune deficiency known as HIV acquired immunodeficiency syndrome (HIV/AIDS). The gut associated lymphoid tissue is one of the major lymphoid tissues targeted by HIV-1, and is considered a reservoir for HIV-1 replication and of major importance in CD4+ T-cell depletion. In addition to immunodeficiency, HIV-1 infection also directly causes gastrointestinal (GI) dysfunction, also known as HIV enteropathy. This enteropathy can manifest itself as many pathological changes in the GI tract. The objective of this study was to determine the association of gut HIV-1 infection markers with long-term survival in a cohort of men who have sex with men (MSM) enrolled pre-HAART (Highly Active Antiretroviral Therapy). We examined survival over 15-years in a cohort of 42 HIV-infected cases: In addition to CD4+ T cell counts and HIV-1 plasma viral load, multiple gut compartment (duodenum and colon) biopsies were taken by endoscopy every 6 months during the initial 3-year period. HIV-1 was cultured from tissues and phenotyped and viral loads in the gut tissues were determined. Moreover, the tissues were subjected to an extensive assessment of enteroendocrine cell distribution and pathology. The collected data was used for survival analyses, which showed that patients with higher gut tissue viral load levels had a significantly worse survival prognosis. Moreover, lower numbers of serotonin (duodenum) and somatostatin (duodenum and colon) immunoreactive cell counts in the gut tissues of patients was associated with significant lower survival prognosis. Our study, suggested that HIV-1 pathogenesis and survival prognosis is associated with altered enteroendocrine cell numbers, which could point to a potential role for enteroendocrine function in HIV infection and pathogenesis. 相似文献
20.
Anne Lamontagne Ronald E. Long Mary Ann Comunale Julie Hafner Lucy Rodemich-Betesh Mengjun Wang Jorge Marrero Adrian M. Di Bisceglie Timothy Block Anand Mehta 《PloS one》2013,8(6)