Circulating Plasmacytoid Dendritic Cells in Acutely Infected Patients with Hepatitis C Virus Genotype 4 Are Normal in Number and Phenotype
ABSTRACT The incidence of hepatitis C virus (HCV) genotype 4 infection in Egypt provides a unique opportunity to study the innate immune response to symptomatic acute HCV infection. We investigated whether plasmacytoid dendritic cells (pDCs) are activated as a result of HCV infection. We demonstrate that, even during symptomatic acute infection, circulating pDCs maintained a similar precursor frequency and resting phenotype, compared with pDCs in healthy individuals. Moreover, stimulation with a Toll-like receptor 9 agonist resulted in an intact inflammatory response. These data support the growing consensus that pDCs are not directly activated by HCV and therefore are viable targets for immunotherapy throughout HCV infection.
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ABSTRACT: BACKGROUND & AIMS: Case definitions for recent hepatitis C virus (HCV) infection vary considerably between studies. The aim of this systematic review was to characterize case definitions for recent HCV and explore the heterogeneity in studies performed to date. METHODS: A systematic literature search of MEDLINE, SCOPUS, and ISI Web of Knowledge was performed covering all studies of recent HCV infection cited between January 2000 and June 2011. The criteria used by each study to define cases of recent HCV infection were extracted, structured, and analyzed. RESULTS: Overall, 195 articles were included, with 87% (n=169) providing a clear case definition for recent HCV infection. The most frequently used individual criteria for defining a case included HCV antibody seroconversion (77%), alanine aminotransferase (ALT) elevation (68%), and HCV RNA detection (63%). In studies using HCV antibody seroconversion, the window period between the last negative and the first positive antibody test varied widely across studies (4weeks to 4years). Considerable diversity was also observed with respect to the ALT threshold used to characterize ALT elevations, ranging from 2 to 20 times the upper limit of normal. HCV antibody seroconversion was used as a single criterion in 41% of the studies, while all other studies used at least two criteria (range: 2-9). Epidemiology/surveillance studies mostly used a more sensitive case definition, whereas treatment studies, natural history studies, and diagnosis studies used more specific case definitions. CONCLUSIONS: Marked heterogeneity in case definitions for recent HCV infection was observed. Although a single case definition for recent HCV is not warranted, a degree of standardization within specific study categories would enable improved cross-study comparison and more uniform evaluation of HCV prevention and management strategies.Journal of Hepatology 07/2012; 57(6). DOI:10.1016/j.jhep.2012.07.007 · 10.40 Impact Factor
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ABSTRACT: Dendritic cells (DCs) play an important role in the induction of the primary immune response to infection. DCs may express the tryptophan-catabolizing enzyme indolamine2,3-dioxygenase (IDO), which is an inducer of immune tolerance. Since there is evidence that chronic hepatitis C virus (HCV) infection leads to functional impairment of certain DC populations, we analyzed IDO expression in DCs and monocytes from chronically infected and recovered HCV patients. The IDO1 and -2 expression was significantly increased in the monocytes of chronic HCV patients, but interestingly, not in those from recovered patients. The myeloid DCs from chronically infected HCV patients also showed enhanced IDO1 expression, while no change in either IDO1 or -2 was found for plasmacytoid DCs. Up-regulation of IDO1 gene expression was confirmed by the presence of enhanced kynurenine/tryptophan ratios in the plasma from chronic HCV patients. Increased IDO1 and IDO2 expression was also observed in monocytes from healthy donors infected with an adapted mutant of JFH1-HCV ex vivo, confirming a direct effect of HCV infection. These changes in IDO expression could be prevented by treatment with the IDO inhibitor 1-methyl tryptophan (1-mT). Furthermore, maturation of monocyte-derived DCs from chronically infected HCV patients, as well as well as monocyte-derived DCs ex vivo infected with HCV, was impaired, but this was reversed by 1-mT treatment. This suggests that IDO inhibitors may be used to treat chronic HCV patients in vivo, in conjunction with current therapies, or to activate DCs from patients ex vivo, such that they can be administered back as a DC-based therapeutic vaccine. This article is protected by copyright. All rights reserved. © 2015 British Society for Immunology.Clinical & Experimental Immunology 01/2015; DOI:10.1111/cei.12586 · 3.28 Impact Factor