Compartmentalized Immune Response in Leishmaniasis: Changing Patterns throughout the Disease

Visceral leishmaniasis (VL) is characterized by loss of T-cell responsiveness and absence of Leishmania-specific IFN-γ production by peripheral blood mononuclear cells. However, the expressions of IFN-γ and TNF-α are up-regulated in the tissues and plasma of VL patients. There is a paucity of information regarding the cytokine profile expressed by different target tissues in the same individual and the changes it undergoes throughout the course of infection. In this work we evaluated IFN-γ, TNF-α, IL-10, and TGF-β mRNA expression using real-time RT-PCR in 5 target tissues at 6 months and 16 months post-infection (PI) in a canine experimental model which mimics many aspects of human VL. The spleen and liver of Leishmania infantum experimentally-infected dogs elicited a pro- and anti- inflammatory response and high parasite density at 6 and 16 months PI. The popliteal lymph node, however, showed an up-regulation of IFN-γ cytokin at commencement of the study and was at the chronic phase when the IL-10 and TGF-β expression appeared. In spite of skin parasite invasion, local cytokine response was absent at 6 months PI. Parasite growth and onset of clinical disease both correlated with dermal up-regulation of all the studied cytokines. Our VL model suggests that central target organs, such as the spleen and liver, present a mixed cytokine immune response early on infection. In contrast, an anti-inflammatory/regulatory immune response in peripheral tissues is activated in the later chronic-patent stages of the disease.This work was funded by Projects AGL2008-00748 and AGL2010-16678-GAN from the Spanish Government, and Grant 2005 FI 01116 from Generalitat de Catalunya Spain.S

Europe and the Nation: Austrian EU-Scepticism and Its Contestation

This discussion of EU-scepticism and its contestation in contemporary Austria is based on a qualitative, discourse analytical reading of the country's diverse media over recent years. Focusing in particular on news coverage and readers' letters pertaining to various (perceived) European crises, the analysis draws on the concepts of topoi (or ‘structures of argument’) and deixis (or ‘rhetorical pointing’) to examine the following four thematic foci, around which different positions of EU-scepticism, pragmatism and pro-European counter-discourses are variously formulated and argued over: the role and effects of (global) markets; a spectrum of competing identifications; frameworks of memory and prediction; debates about the EU's institutional structures and different political visions. The internally heterogeneous and strongly contested discursive field thus revealed also demonstrates the uneasy coexistence of various, more or less rigid discourses of national identity with emerging forms of ‘banal Europeanism’. While focused on Austrian data throughout, this analysis also points towards discursive parallels in other parts of the EU and argues for the value of qualitative analyses of EU-scepticism and its counter-discourses to complement existing quantitative studies