Role of the Chemokine Receptors CCR1, CCR2 and CCR4 in the Pathogenesis of Experimental Dengue Infection in Mice

Dengue virus (DENV), a mosquito-borne flavivirus, is a public health problem in many tropical countries. Recent clinical data have shown an association between levels of different chemokines in plasma and severity of dengue. We evaluated the role of CC chemokine receptors CCR1, CCR2 and CCR4 in an experimental model of DENV-2 infection in mice. Infection of mice induced evident clinical disease and tissue damage, including thrombocytopenia, hemoconcentration, lymphopenia, increased levels of transaminases and pro-inflammatory cytokines, and lethality in WT mice. Importantly, infected WT mice presented increased levels of chemokines CCL2/JE, CCL3/MIP-1α and CCL5/RANTES in spleen and liver. CCR1-/- mice had a mild phenotype with disease presentation and lethality similar to those of WT mice. In CCR2-/- mice, lethality, liver damage, levels of IL-6 and IFN-γ, and leukocyte activation were attenuated. However, thrombocytopenia, hemoconcentration and systemic TNF-α levels were similar to infected WT mice. Infection enhanced levels of CCL17/TARC, a CCR4 ligand. In CCR4-/- mice, lethality, tissue injury and systemic inflammation were markedly decreased. Despite differences in disease presentation in CCR-deficient mice, there was no significant difference in viral load. In conclusion, activation of chemokine receptors has discrete roles in the pathogenesis of dengue infection. These studies suggest that the chemokine storm that follows severe primary dengue infection associates mostly to development of disease rather than protection

He atom scattering from ZnO surfaces: Calculation of diffraction peak intensities using the close-coupling approach

Diffraction intensities of a molecular He beam scattered off the clean and water-covered ZnO(10 1̄0) surface have been simulated using a new potential model in conjunction with the close-coupling formalism. The effective corrugation functions for the systems He-ZnO(10 l̄0) and He-H 2O/ZnO(10 1̄0) have been obtained from density functional theory calculations within the Esbjerg-Nørskov approximation. Using these data a potential model is constructed consisting of a corrugated Morse potential at small He-surface distances and a semiempiric attractive part at larger distances. The diffraction patterns obtained from close-coupling calculations agree with the experimental data within about 10%, which opens the possibility to simulate He diffraction from surfaces of any structural complexity and to verify surface and adsorbate structures proposed theoretically by employing this kind of analysis. © 2010 IOP Publishing Ltd.This work was supported in part by DGCYT (Spain) under project FIS2007-62006 and by DFG (Germany) within the Collaborative Research Center SFB 558 ‘Metal–substrate interactions in heterogeneous catalysis’. RM-C would like to thank the Royal Society for a Newton Fellowship.Peer Reviewe

Diffraction patterns of He atoms from the MgO(100) surface calculated by the close-coupling method

An analysis of He diffraction data for the MgO(001) surface which goes beyond hard-wall eikonal approximations is presented. In a first step, a model potential, for which the form of a corrugated Morse potential is chosen, is set up using the eikonal approximation in connection with an effective corrugation function. The obtained corrugation amplitude is compared to results from density-functional theory calculations of the He-MgO interaction. In a second step, this model potential is used for close-coupling (CC) calculations of He diffraction intensities. A kinematical analysis of the system He/MgO is given. The results on the He diffraction intensities are in good agreement with the experiment. © IOP Publishing Ltd.Peer Reviewe