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Hôpital-Camfrout, France

Fregni G.,French Institute of Health and Medical Research | Fregni G.,University of Paris Descartes | Fregni G.,University of Lausanne | Freire Maresca A.,Service de Medecine Interne | And 12 more authors.
Virology Journal

Background: Both the human immunodeficiency virus (HIV) and hepatitis C virus (HCV), either alone or as coinfections, persist in their hosts by destroying and/or escaping immune defenses, with high morbidity as consequence. In some cases, however, a balance between infection and immunity is reached, leading to prolonged asymptomatic periods. We report a case of such an indolent co-infection, which could be explained by the development of a peculiar subset of Natural Killer (NK) cells. Results: Persistently high peripheral levels of CD56+ NK cells were observed in a peculiar hemophiliac HIV/HCV co-infected patient with low CD4 counts, almost undetectable HIV viral load and no opportunistic infections. Thorough analysis of NK-subsets allowed to identify a marked increase in the CD56bright/dim cell ratio and low numbers of CD16+/CD56- cells. These cells have high levels of natural cytotoxicity receptors but low NCR2 and CD69, and lack both CD57 and CD25 expression. The degranulation potential of NK-cells which correlates with target cytolysis was atypically mainly performed by CD56bright NK-cells, whereas no production of interferon γ (IFN-γ) was observed following NK activation by K562 cells. Conclusions: These data suggest that the expansion and lytic capacity of the CD56bright NK subset may be involved in the protection of this " rare " HIV/HCV co-infected hemophiliac A patient from opportunistic infections and virus-related cancers despite very low CD4+ cell counts. © 2013 Fregni et al. Source

Borgel D.,Service dHematologie et dImmunologie | Borgel D.,University Paris - Sud | Vieillard-Baron A.,Service de Reanimation medicale

Sepsis is defined as a systemic response to infection, characterized by an intense inflammatory response linked to coagulation activation and fibrinolysis inhibition, two processes which are intimately associated. In a field where mortality remains very high, administration of activated protein C, a physiological coagulation inhibitor with cytoprotective properties, has demonstrated its effectiveness and was able to reduce mortality. Protein C belongs to a system that involves plasma proteins and endothelial cell receptors. In addition to well documented effects on coagulation and fibrinolysis, activated protein C exhibits anti-inflammatory, anti-apoptotic but also anti-histone activities. Indeed, a recent study focusing on the cytoprotective effects of activated protein C showed that extracellular histones are released during severe sepsis and may participate in the pathophysiology of severe sepsis. These histones appear to be new targets of activated protein C. Source

Borgel D.,Service dHematologie et dImmunologie | Borgel D.,University Paris - Sud | Lerolle N.,Angers University Hospital Center

Treatment of severe sepsis with activated protein C (Xigris®) has generated great hopes but has also been a subject of controversy. The rational for its evaluation in this indication was based on the increasing knowledge regarding severe sepsis pathophysiology, which has clearly highlighted a reciprocal runaway between inflammation and coagulation processes in these patients. Activated protein C, like other coagulation inhibitors, possesses anti-inflammatory properties in addition to their anticoagulant activity, making them attractive candidates in this indication. However, after Xigris® withdrawal and the negative results of phase III trials evaluating two other inhibitors, tissue factor pathway inhibitor (TFPI) and antithrombin, is there still a place for new drugs targeting haemostasis? The use of soluble thrombomodulin, development of optimized variants of activated protein C as well as inhibitors of both tissue factor-FVIIa and FXIIa-FXIa axes are currently under evaluation. © 2013 Société de réanimation de langue française (SRLF) and Springer-Verlag France. Source

Flaujac C.,Service dHematologie et dImmunologie | Flaujac C.,University of Versailles | Flaujac C.,French Institute of Health and Medical Research | Boukour S.,Service dHematologie et dImmunologie | And 5 more authors.
Cellular and Molecular Life Sciences

Thrombocytopenia is a frequent complication of viral infections providing evidence that interaction of platelets with viruses is an important pathophysiological phenomenon. Multiple mechanisms are involved depending on the nature of the viruses involved. These include immunological platelet destruction, inappropriate platelet activation and consumption, and impaired megakaryopoiesis. Viruses bind platelets through specific receptors and identified ligands, which lead to mutual alterations of both the platelet host and the viral aggressor. We have shown that HIV-1 viruses are internalized specifically in platelets and megakaryocytes, where they can be either sheltered, unaltered (with potential transfer of the viruses into target organs), or come in contact with platelet secretory products leading to virus destruction and facilitated platelet clearance. In this issue, we have reviewed the various pathways that platelets use in order to interact with viruses, HIV and others. This review also shows that more work is still needed to precisely identify platelet roles in viral infections, and to answer the challenge of viral safety in platelet transfusion. © 2009 Birkhäuser Verlag, Basel/Switzerland. Source

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