Polyfunctional T cell responses in children in early stages of chronic Trypanosoma cruzi infection contrast with monofunctional responses of long-term infected adults

Background: Adults with chronic Trypanosoma cruzi exhibit a poorly functional T cell compartment, characterized by monofunctional (IFN-γ-only secreting) parasite-specific T cells and increased levels of terminally differentiated T cells. It is possible that persistent infection and/or sustained exposure to parasites antigens may lead to a progressive loss of function of the immune T cells. Methodology/Principal Findings: To test this hypothesis, the quality and magnitude of T. cruzi-specific T cell responses were evaluated in T. cruzi-infected children and compared with long-term T. cruzi-infected adults with no evidence of heart failure. The phenotype of CD4+ T cells was also assessed in T. cruzi-infected children and uninfected controls. Simultaneous secretion of IFN-γ and IL-2 measured by ELISPOT assays in response to T. cruzi antigens was prevalent among T. cruzi-infected children. Flow cytometric analysis of co-expression profiles of CD4+ T cells with the ability to produce IFN-γ, TNF-α, or to express the co-stimulatory molecule CD154 in response to T. cruzi showed polyfunctional T cell responses in most T. cruzi-infected children. Monofunctional T cell responses and an absence of CD4+TNF-α+-secreting T cells were observed in T. cruzi-infected adults. A relatively high degree of activation and differentiation of CD4+ T cells was evident in T. cruzi-infected children. Conclusions/Significance: Our observations are compatible with our initial hypothesis that persistent T. cruzi infection promotes eventual exhaustion of immune system, which might contribute to disease progression in long-term infected subjects.Fil: Albareda, María Cecilia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: de Rissio, Ana María. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Tomas, Gonzalo. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Serjan, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Alvarez, María Gabriela. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Viotti, Rodolfo Jorge. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Fichera, Laura Edith. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Esteva, Mónica Inés. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Potente, Daniel Fernando. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Armenti, Alejandro. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Tarleton, Rick L.. University of Georgia; Estados UnidosFil: Laucella, Susana Adriana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

A unifying perspective on protocol mediation: interoperability in the Future Internet

Given the highly dynamic and extremely heterogeneous software systems composing the Future Internet, automatically achieving interoperability between software components —without modifying them— is more than simply desirable, it is quickly becoming a necessity. Although much work has been carried out on interoperability, existing solutions have not fully succeeded in keeping pace with the increasing complexity and heterogeneity of modern software, and meeting the demands of runtime support. On the one hand, solutions at the application layer target higher automation and loose coupling through the synthesis of intermediary entities, mediators, to compensate for the differences between the interfaces of components and coordinate their behaviours, while assuming the use of the same middleware solution. On the other hand, solutions to interoperability across heterogeneous middleware technologies do not reconcile the differences between components at the application layer. In this paper we propose a unified approach for achieving interoperability between heterogeneous software components with compatible functionalities across the application and middleware layers. First, we provide a solution to automatically generate cross-layer parsers and composers that abstract network messages into a uniform representation independent of the middleware used. Second, these generated parsers and composers are integrated within a mediation framework to support the deployment of the mediators synthesised at the application layer. More specifically, the generated parser analyses the network messages received from one component and transforms them into a representation that can be understood by the application-level mediator. Then, the application-level mediator performs the necessary data conversion and behavioural coordination. Finally, the composer transforms the representation produced by the application-level mediator into network messages that can be sent to the other component. The resulting unified mediation framework reconciles the differences between software components from the application down to the middleware layers. We validate our approach through a case study in the area of conference management

Isospin violating dark matter in Stückelberg portal scenarios

Journal of High Energy Physics 2015.4 (2015): 175 reproduced by permission of Scuola Internazionale Superiore di Studi Avanzati (SISSA)Hidden sector scenarios in which dark matter (DM) interacts with the Standard Model matter fields through the exchange of massive Z′ bosons are well motivated by certain string theory constructions. In this work, we thoroughly study the phenomenological aspects of such scenarios and find that they present a clear and testable consequence for direct DM searches. We show that such string motivated Stückelberg portals naturally lead to isospin violating interactions of DM particles with nuclei. We find that the relations between the DM coupling to neutrons and protons for both, spin-independent (fn/fp) and spin-dependent (an/ap) interactions, are very flexible depending on the charges of the quarks under the extra U(1) gauge groups. We show that within this construction these ratios are generically different from ±1 (i.e. different couplings to protons and neutrons) leading to a potentially measurable distinction from other popular portals. Finally, we incorporate bounds from searches for dijet and dilepton resonances at the LHC as well as LUX bounds on the elastic scattering of DM off nucleons to determine the experimentally allowed values of fn/fp and an/apThe authors are grateful to D. G. Cerdeño, L. Ibañez, F. Kahlhoefer and G. Shiu for useful comments. V.M.L. and M.P. would like to thank the support of the European Union under the ERC Advanced Grant SPLE under contract ERC-2012-ADG-20120216-320421, the support of the Consolider-Ingenio 2010 programme under grant MULTIDARK CSD2009-00064, the Spanish MICINN under Grant No. FPA2012-34694, the Spanish MINECO “Centro de excelencia Severo Ochoa Program” under Grant No. SEV-2012-0249, and the Community of Madrid under Grant No. HEPHACOS S2009/ESP-1473. P.S. would like to thank DESY, the University of Hamburg, and the Hong Kong IAS for kind hospitality during the completion of this work. He acknowledges support from the DOE grant DEFG-02-95ER40896 and the HKRGC grant HKUST4/CRF/13G, 604231, as well as the Collaborative Research Center SFB676 of the DFG at the University of Hambur

Identification of Mycobacterium tuberculosis-Specific Th1, Th17 and Th22 Cells Using the Expression of CD40L in Tuberculous Pleurisy

Important advances have been made in the immunodiagnosis of tuberculosis (TB) based on the detection of Mycobacterium tuberculosis (MTB)-specific T cells. However, the sensitivity and specificity of the immunological approach are relatively low because there are no specific markers for antigen-specific Th cells, and some of the Th cells that do not produce cytokines can be overlooked using this approach. In this study, we found that MTB-specific peptides of ESAT-6/CFP-10 can stimulate the expression of CD40L specifically in CD4+ T cells but not other cells from pleural fluid cells (PFCs) in patients with tuberculous pleurisy (TBP). CD4+CD40L+ but not CD4+CD40L− T cells express IFN-γ, IL-2, TNF-α, IL-17 or IL-22 after stimulation with MTB-specific peptides. In addition, CD4+CD40L+ T cells were found to be mostly polyfunctional T cells that simultaneously produce IFN-γ, IL-2 and TNF-α and display an effector or effector memory phenotype (CD45RA−CD45RO+CCR7−CD62L−ICOS−). To determine the specificity of CD4+CD40L+ T cells, we incubated PFCs with ESTA-6/CFP-10 peptides and sorted live CD4+CD40L+ and CD4+CD40L− T cells by flow cytometry. We further demonstrated that sorted CD4+CD40L+, but not CD4+CD40L− fractions, principally produced IFN-γ, IL-2, TNF-α, IL-17 and IL-22 following restimulation with ESTA-6/CFP-10 peptides. Taken together, our data indicate that the expression of CD40L on MTB-specific CD4+ T cells could be a good marker for the evaluation and isolation of MTB-specific Th cells and might also be useful in the diagnosis of TB