Antiviral antibodies target adenovirus to phagolysosomes and amplify the innate immune response.

Adenovirus is a nonenveloped dsDNA virus that activates intracellular innate immune pathways. In vivo, adenovirus-immunized mice displayed an enhanced innate immune response and diminished virus-mediated gene delivery following challenge with the adenovirus vector AdLacZ suggesting that antiviral Abs modulate viral interactions with innate immune cells. Under naive serum conditions in vitro, adenovirus binding and internalization in macrophages and the subsequent activation of innate immune mechanisms were inefficient. In contrast to the neutralizing effect observed in nonhematopoietic cells, adenovirus infection in the presence of antiviral Abs significantly increased FcR-dependent viral internalization in macrophages. In direct correlation with the increased viral internalization, antiviral Abs amplified the innate immune response to adenovirus as determined by the expression of NF-kappaB-dependent genes, type I IFNs, and caspase-dependent IL-1beta maturation. Immune serum amplified TLR9-independent type I IFN expression and enhanced NLRP3-dependent IL-1beta maturation in response to adenovirus, confirming that antiviral Abs specifically amplify intracellular innate pathways. In the presence of Abs, confocal microscopy demonstrated increased targeting of adenovirus to LAMP1-positive phagolysosomes in macrophages but not epithelial cells. These data show that antiviral Abs subvert natural viral tropism and target the adenovirus to phagolysosomes and the intracellular innate immune system in macrophages. Furthermore, these results illustrate a cross-talk where the adaptive immune system positively regulates the innate immune system and the antiviral state.

Reliure de : Martialis Epigrammata. - "Fol. A i, r°" : Martialis. - "Fol. A i, v°" : Plinius junior Cornelio Prisco, s. - "Fol. A ii" : M. V. Martialis Epigrammata. - "A la fin" : Venetiis, in aedibus Aldi, mense decembri MDI. Quisquis es qui quoquo modo hujusce excusionis ergo adversus ieris, damnatus esto et reus. III. s. v. ne dicas tibi non praedictum. Cave

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Incidence and mechanisms of cerebral ischemia in early clinical head injury.

Antemortem demonstration of ischemia has proved elusive in head injury because regional CBF reductions may represent hypoperfusion appropriately coupled to hypometabolism. Fifteen patients underwent positron emission tomography within 24 hours of head injury to map cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2), and oxygen extraction fraction (OEF). We estimated the volume of ischemic brain (IBV) and used the standard deviation of the OEF distribution to estimate the efficiency of coupling between CBF and CMRO2. The IBV in patients was significantly higher than controls (67 +/- 69 vs. 2 +/- 3 mL; P < 0.01). The coexistence of relative ischemia and hyperemia in some patients implies mismatching of perfusion to oxygen use. Whereas the saturation of jugular bulb blood (SjO2) correlated with the IBV (r = 0.8, P < 0.01), SjO2 values of 50% were only achieved at an IBV of 170 +/- 63 mL (mean +/- 95% CI), which equates to 13 +/- 5% of the brain. Increases in IBV correlated with a poor Glasgow Outcome Score 6 months after injury (rho = -0.6, P < 0.05). These results suggest significant ischemia within the first day after head injury. The ischemic burden represented by this "traumatic penumbra" is poorly detected by bedside clinical monitors and has significant associations with outcome.

[Captain Richard Francis Burton] / A. Claudet

Donateur : Jackson, James (1843-1895)

Precision determination of r(0)Lambda((MS)over-bar) from the QCD static energy

We use the recently obtained theoretical expression for the complete QCD static energy at next-to-next-to-next-to leading-logarithmic accuracy to determine r(0)Lambda((MS) over bar) by comparison with available lattice data, where r(0) is the lattice scale and Lambda((MS) over bar) is the QCD scale. We obtain r(0)Lambda((MS) over bar) = 0.622(-0.015)(+0.019) for the zero-flavor case. The procedure we describe can be directly used to obtain r(0)Lambda((MS) over bar) in the unquenched case, when unquenched lattice data for the static energy at short distances becomes available. Using the value of the strong coupling alpha(s) as an input, the unquenched result would provide a determination of the lattice scale r(0).