1,720,964 research outputs found
Diet-related inflammation and immune dysfunction in obesity: potential risk factors for colorectal cancer
No full textInterplay between hiv-1 and toll-like receptors in human myeloid cells: Friend or foe in hiv-1 pathogenesis?
No full textThe Toll-like receptors are the first line of the host
response to pathogens, representing an essential com-
ponent of the innate and adaptive immune response.
They recognize different pathogens and trigger re-
sponses directed at eliminating the invader and at de-
veloping immunologic long-term memory, ultimately
affecting viral pathogenesis. In viral infections, sensing of
nucleic acids and/or viral structural proteins generally
induces a protective immune response. Thus, it is not
surprising that many viruses have developed strategies
to evade or counteract signaling through the Toll-like
receptor pathways, to survive the host defense machin-
ery and ensure propagation. Thus, Toll-like receptor
engagement can also be part of viral pathogenic mech-
anisms. Evidence for a direct interaction of Toll-like
receptors with human immunodeficiency virus type 1
(HIV-1) structures has started to be achieved, and
alterations of their expression and function have been
described in HIV-1–positive subjects. Furthermore, Toll-
like receptor triggering by bacterial and viral ligands have
been described to modulate HIV-1 replication and host
response, leading to protective or detrimental effects.
This review covers major advances in the field of HIV-1
interplay with Toll-like receptors, focusing on human
myeloid cells (e.g., monocytes/macrophages and den-
dritic cells). The role of this interaction in the dysregula-
tion of myeloid cell function and in dictating aspects of
the multifaceted pathogenesis of acquired immunodefi-
ciency syndrome will be discusse
Immunomodulatory effects of HIV-1 gp120 on human dendritic cells: role of STAT3/IL-6 axis
No full textThe ability of HIV-1 to exploit the host immune responses to its own advantage is critical in the pathogenesis of AIDS. Since dendritic cells (DCs) are key players in the induction of immune responses, the modulation of their functional activities represents a strategic mechanism for HIV-1 to evade immune surveillance. In this study, we report that exposure of immature monocyte-derived DCs (MDDCs) to recombinant gp120 transcriptionally activates IL-6 expression and promotes its secretion in a concentration and time-dependent manner. Activation of MAPK p38 is involved in gp120 triggered IL-6 over-expression as p38 specific inhibitors markedly reduced IL-6 secretion. IL-6 over-expression induces at later time points accumulation of the tyrosine phosphorylated form of STAT3. Blocking IL-6 biological activity resulted in a dramatic reduction of STAT3 activation suggesting that gp120 might interfere with the STAT3/IL-6 axis. Consistently with this hypothesis, blocking STAT3 activation markedly decreases IL-6 secretion. Reconstruction of the signaling pathway triggered by gp120 in MDDCs unraveled a biphasic activation of STAT3, triggered early on by gp120 and leading to IL-6 secretion which, at later time points, induces a second round of STAT3 activation. Moreover, the possible involvement of cellular microRNAs in the regulation of this process will be discussed. Overall, these results indicate that DCs may contribute to the up-modulation of IL-6 found in HIV infected individuals. Furthermore, chronic activation of STAT3 in DCs may provide an explanation for the impairment of DC function
HIV-1 gp120 influences the expression of microRNAs in human monocyte-derived dendritic cells via STAT3 activation
Get PDFBackground:
MicroRNAs (miRs) are an abundant class of small non-coding RNAs (~22 nt) that reprogram gene ex-
pression by targeting mRNA degradation and translational disruption. An emerging concept implicates miR coup-
ling with transcription factors in myeloid cell development and function, thus contributing to host defense and
inflammation. The important role that these molecules play in the pathogenesis of HIV-1 is only now emerging.
Results:
We provide evidence that exposure of monocyte-derived dendritic cells (MDDCs) to recombinant HIV-1 R5
gp120, but not to CCR5 natural ligand CCL4, influences the expression of a panel of miRs (i.e., miR-21, miR-155 and
miR-181b) regulated by STAT3 and potentially targeting genes belonging to the STAT3 signaling pathway. The
blockage of gp120-induced STAT3 activation impairs gp120 capacity to modulate the expression level of above
mentioned miRs. Predictive analysis of miR putative targets emphasizes that these miRs share common target
genes. Furthermore, gene ontology and pathway enrichment analysis outline that these genes mainly belong to
biological processes related to regulation of transcription, in a complex network of interactions involving pathways
relevant to HIV-DC interaction.
Conclusions:
Overall, these results point to gp120-triggered modulation of miR expression via STAT3 activation as a
novel molecular mechanism exploited by HIV-1 to affect DC biology and thus modulate the immune response
through complex regulatory loops involving, at the same time, miRs and transcription factors
Hiv-1 gp120 activates the stat3/interleukin-6 axis in primary human monocyte-derived dendritic cells
No full textDendritic cells (DCs) are fundamental for the initiation of immune responses and are important players in AIDS immunopathogenesis. The modulation of DC functional activities represents a strategic mechanism for HIV-1 to evade immune surveillance. Impairment of DC function may result from bystander effects of HIV-1 envelope proteins independently of direct HIV-1 infection.
In this study, we report that exposure of immature monocyte-derived DCs (MDDCs) to HIV-1 R5 gp120 resulted in the CCR5-dependent production of IL-6 via MAPK/NF-kB pathways. IL-6 in turn activated STAT3 by an autocrine loop. Concomitantly, gp120 promoted an early activation of STAT3 that further contributed to IL-6 induction. This activation paralleled a concomitant up-regulation of the STAT3 inhibitor PIAS3. Furthermore, the STAT3-regulated microRNAs (miRs) miR-21, miR-155 and miR-181b, were found to be modulated upon gp120 exposure of MDDCs. Notably, neither STAT3/IL-6 pathway activation nor miRs modulation were affected by the CCR5 specific ligand CCL4. Gene ontology and pathway enrichment analysis of functionally relevant targets outlined that these miRs shared common target genes. Furthermore, many of these genes had a fundamental role in the regulation of transcription, and were potentially relevant for the interaction between HIV and DCs.
These results identify STAT3 as a key signaling intermediate activated by gp120 in MDDCs and highlight the existence of a novel regulatory network involving STAT3, IL-6 and miRs. HIV-1 gp120 signaling through STAT3 may provide an explanation for the impairment of DC function observed upon HIV exposure
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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