Activation of a dendritic cell–T cell axis by Ad5 immune complexes creates an improved environment for replication of HIV in T cells

The STEP HIV vaccine trial, which evaluated a replication-defective adenovirus type 5 (Ad5) vector vaccine, was recently stopped. The reasons for this included lack of efficacy of the vaccine and a twofold increase in the incidence of HIV acquisition among vaccinated recipients with increased Ad5-neutralizing antibody titers compared with placebo recipients. To model the events that might be occurring in vivo, the effect on dendritic cells (DCs) of Ad5 vector alone or treated with neutralizing antiserum (Ad5 immune complexes [IC]) was compared. Ad5 IC induced more notable DC maturation, as indicated by increased CD86 expression, decreased endocytosis, and production of tumor necrosis factor and type I interferons. We found that DC stimulation by Ad5 IC was mediated by the Fcγ receptor IIa and Toll-like receptor 9 interactions. DCs treated with Ad5 IC also induced significantly higher stimulation of Ad5-specific CD8 T cells equipped with cytolytic machinery. In contrast to Ad5 vectors alone, Ad5 IC caused significantly enhanced HIV infection in DC–T cell cocultures. The present results indicate that Ad5 IC activates a DC–T cell axis that, together with the possible persistence of the Ad5 vaccine in seropositive individuals, may set up a permissive environment for HIV-1 infection, which could account for the increased acquisition of HIV-1 infection among Ad5 seropositive vaccine recipients

Activation of a dendritic cell–T cell axis by Ad5 immune complexes creates an improved environment for replication of HIV in T cells

The STEP HIV vaccine trial, which evaluated a replication-defective adenovirus type 5 (Ad5) vector vaccine, was recently stopped. The reasons for this included lack of efficacy of the vaccine and a twofold increase in the incidence of HIV acquisition among vaccinated recipients with increased Ad5-neutralizing antibody titers compared with placebo recipients. To model the events that might be occurring in vivo, the effect on dendritic cells (DCs) of Ad5 vector alone or treated with neutralizing antiserum (Ad5 immune complexes [IC]) was compared. Ad5 IC induced more notable DC maturation, as indicated by increased CD86 expression, decreased endocytosis, and production of tumor necrosis factor and type I interferons. We found that DC stimulation by Ad5 IC was mediated by the Fcγ receptor IIa and Toll-like receptor 9 interactions. DCs treated with Ad5 IC also induced significantly higher stimulation of Ad5-specific CD8 T cells equipped with cytolytic machinery. In contrast to Ad5 vectors alone, Ad5 IC caused significantly enhanced HIV infection in DC–T cell cocultures. The present results indicate that Ad5 IC activates a DC–T cell axis that, together with the possible persistence of the Ad5 vaccine in seropositive individuals, may set up a permissive environment for HIV-1 infection, which could account for the increased acquisition of HIV-1 infection among Ad5 seropositive vaccine recipients

La méthode d'immunofluorescence et l'identification des mycoplasmes. Application au diagnostic de la péripneumonie

L'application de la méthode d'immunofluorescence à l'identification des mycoplasmes et en particulier à la recherche de M. mycoïdes, dans les cultures comme dans les exsudats pathologiques et les lésions, est effectuée par les procédés classiques en utilisant soit des sérums expérimentaux anti-mycoïdes, soit des sérums de bovins malades naturels. Les résultats montrent que ce procédé est spécifique et que des réactions croisées ne sont pas à craindre avec les autres espèces de mycoplasmes rencontrées chez les ruminants si l'on s'entoure d'un minimum de précautions. Les conditions techniques de ces examens font l'objet d'une description détaillé

IRF5 Is a Key Regulator of Macrophage Response to Lipopolysaccharide in Newborns.

Infections are a leading cause of mortality and morbidity in newborns. The high susceptibility of newborns to infection has been associated with a limited capacity to mount protective immune responses. Monocytes and macrophages are involved in the initiation, amplification, and termination of immune responses. Depending on cues received from their environment, monocytes differentiate into M1 or M2 macrophages with proinflammatory or anti-inflammatory and tissue repair properties, respectively. The purpose of this study was to characterize differences in monocyte to macrophage differentiation and polarization between newborns and adults. Monocytes from umbilical cord blood of healthy term newborns and from peripheral blood of adult healthy subjects were exposed to GM-CSF or M-CSF to induce M1 or M2 macrophages. Newborn monocytes differentiated into M1 and M2 macrophages with similar morphology and expression of differentiation/polarization markers as adult monocytes, with the exception of CD163 that was expressed at sevenfold higher levels in newborn compared to adult M1 macrophages. Upon TLR4 stimulation, newborn M1 macrophages produced threefold to sixfold lower levels of TNF than adult macrophages, while production of IL-1-β, IL-6, IL-8, IL-10, and IL-23 was at similar levels as in adults. Nuclear levels of IRF5, a transcription factor involved in M1 polarization, were markedly reduced in newborns, whereas the NF-κB and MAP kinase pathways were not altered. In line with a functional role for IRF5, adenoviral-mediated IRF5 overexpression in newborn M1 macrophages restored lipopolysaccharide-induced TNF production. Altogether, these data highlight a distinct immune response of newborn macrophages and identify IRF5 as a key regulator of macrophage TNF response in newborns

A Metal-Polymer Interface Study using Electropolymerized Acrylonitrile on Nickel Surfaces

Studies of the interface between mineral and organic materials have been realized for a couple formed between pure transition metal and a polar and polarizable molecule (acrylonitrile). The results presented show the effects of a local electric field on the activation processes associated with adsorption sites and the molecule, interaction mechanisms and the resulting types of chemical bond. The structural, electronic and chemical properties of a nickel-polyacrylonitrile interface are described. Molecular and energetic qualitative models for the interaction mechanisms are proposed

A relative version of Daugavet-points and the Daugavet property

We introduce relative versions of Daugavet-points and the Daugavet property, where the Daugavet-behavior is localized inside of some supporting slice. These points present striking similarities with Daugavet-points, but lie strictly between the notions of Daugavet- and $\Delta$-points. We provide a geometric condition that a space with the Radon--Nikod\'{y}m property must satisfy in order to be able to contain a relative Daugavet-point. We study relative Daugavet-points in absolute sums of Banach spaces, and obtain positive stability results under local polyhedrality of the underlying absolute norm. We also get extreme differences between the relative Daugavet property, the Daugavet property, and the diametral local diameter 2 property. Finally, we study Daugavet- and $\Delta$-points in subspaces of $L_1(\mu)$-spaces. We show that the two notions coincide in the class of all Lipschitz-free spaces over subsets of $\mathbb{R}$-trees. We prove that the diametral local diameter 2 property and the Daugavet property coincide for arbitrary subspaces of $L_1(\mu)$, and that reflexive subspaces of $L_1(\mu)$ do not contain $\Delta$-points. A subspace of $L_1[0,1]$ with a large subset of $\Delta$-points, but with no relative Daugavet-point, is constructed.Comment: 45 pages, 6 figure