In Vitro Derived Dendritic Cells trans-Infect CD4 T Cells Primarily with Surface-Bound HIV-1 Virions

In the prevailing model of HIV-1 trans-infection, dendritic cells (DCs) capture and internalize intact virions and transfer these virions to interacting T cells at the virological synapse. Here, we show that HIV-1 virions transmitted in trans from in vitro derived DCs to T cells principally originate from the surface of DCs. Selective neutralization of surface-bound virions abrogated trans-infection by monocyte-derived DCs and CD34-derived Langerhans cells. Under conditions mimicking antigen recognition by the interacting T cells, most transferred virions still derived from the cell surface, although a few were transferred from an internal compartment. Our findings suggest that attachment inhibitors could neutralize trans-infection of T cells by DCs in vivo

The Achilles Heel of the Trojan Horse Model of HIV-1 trans-Infection

To ensure their survival, microbial pathogens have evolved diverse strategies to subvert host immune defenses. The human retrovirus HIV-1 has been proposed to hijack the natural endocytic function of dendritic cells (DCs) to infect interacting CD4 T cells in a process termed trans-infection. Although DCs can be directly infected by certain strains of HIV-1, productive infection of DCs is not required during trans-infection; instead, DCs capture and internalize infectious HIV-1 virions in vesicles for later transmission to CD4 T cells via vesicular exocytosis across the infectious synapse. This model of sequential endocytosis and exocytosis of intact HIV-1 virions has been dubbed the “Trojan horse” model of HIV-1 trans-infection. While this model gained rapid favor as a strong example of how a pathogen exploits the natural properties of its cellular host, our recent studies challenge this model by showing that the vast majority of virions transmitted in trans originate from the plasma membrane rather than from intracellular vesicles. This review traces the experimental lines of evidence that have contributed to what we view as the “rise and decline” of the Trojan horse model of HIV-1 trans-infection

Optical Oxygen Sensor Patch Printed with Polystyrene Microparticles-Based Ink on Flexible Substrate

Optical oxygen sensors based on photoluminescence quenching have gained increasing attention as a superior method for continuous monitoring of oxygen in a growing number of applications. A simple and low-cost fabrication technique was developed to produce sensor arrays capable of two-dimensional oxygen tension measurement. Sensor patches were printed on polyvinylidene chloride film using an oxygen-sensitive ink cocktail, prepared by immobilizing Pt (II) meso-tetra(pentafluorophenyl)porphine (PtTFPP) in monodispersed polystyrene microparticles. The dispersion media of the ink cocktail, high molecular weight polyvinyl pyrrolidone suspended in 50% ethanol (v/v in water), allowed adhesion promotion and compatibility with most common polymeric substrates. Ink phosphorescence intensity was found to vary primarily with fluorophore concentration and to a lesser extent with polystyrene particle size. The sensor performance was investigated as a function of oxygen concentrations employing two different techniques: a multi-frequency phase fluorometer and smart phone-based image acquisition. The printed sensor patch showed fast and repetitive response over 0-21% oxygen concentrations with high linearity (with R2 \u3e 0.99) in a Stern-Volmer plot, and sensitivity of I0/I21 \u3e 1.55. The optical sensor response on a surface was investigated further using two-dimensional images which were captured and analyzed under different oxygen environment. Printed sensor patch along with imaging read-out technique make an ideal platform for early detection of surface wounds associated with tissue oxygen

Aridity, availability of drinking water and freshwater foods, and hominin and archeological sites during the Late Pliocene-Early Pleistocene in the western region of the Turkana Basin (Kenya): A review

International audienceAlthough the Turkana Basin is one of the driest regions of the East African Rift, its Plio-Pleistocene sediments are rich in freshwater vertebrates and invertebrates, providing evidence that freshwater resources were available to hominins in this region during the Plio-Pleistocene (4.2-0.7 Ma). Here we provide an overview of the hydroconnectivity of the Turkana Basin. We then review the period during which freshwater river and lake systems expanded into the western region of the Turkana Basin, where hominin and archeological sites have been discovered in sediments dating back to the Late Pliocene-Pleistocene. Freshwater conditions are reconstructed from river and lake sediments and the flora and micro-and macofauna they contain. Data synthesis suggests that drinking water and freshwater foods prevailed in the western region of the Turkana Basin at 4. 20-3.98 Ma, 3.70-3.10 Ma, 2.53-2.22 Ma, then between 2.10 and 1.30 Ma and intermittently from 1.27 to 0.75 Ma. Mile-stones in hominin evolution occurred in this context, such as the first occurrence of Australopithecus anamensis (4.20-4.10 Ma) and Kenyanthropus platyops (3.50 Ma and 3.30-3.20 Ma), the presence of Paranthropus aethiopicus (2.53-2.45 Ma), early Homo (2.33 Ma), Paranthropus boisei (2.25 Ma and 1.77-1.72 Ma) and Homo ergaster/Homo erectus (1.75 Ma, 1.47-1.42 Ma and 1.10-0.90 Ma). Developments in hominin behavior also occurred during this timeframe, including the first known stone tools (3.30 Ma), the oldest Oldowan sites (2.34 Ma and 2.25 Ma) in the Turkana Basin, the earliest known evidence for the emergence of bifacial shaping in eastern Africa (1.80 Ma), and the first known Acheulean site (1.76 Ma). Our synthesis suggests that, diachronic variation in hydro-connectivity played a role on the amount of drinking water and freshwater foods available in the western region of the Turkana Basin, despite regional aridity

Immune complex relay by subcapsular sinus macrophages and noncognate B cells drives antibody affinity maturation

Subcapsular sinus (SCS) macrophages capture antigens from lymph and present them intact for B cell encounter and follicular delivery. However, the properties of SCS macrophages are poorly defined. Here we show SCS macrophage development depended on lymphotoxin-α1β2 and the cells had low lysosomal enzyme expression and retained opsonized antigens on their surface. Intravital imaging revealed immune complexes moving along macrophage processes into the follicle. Moreover, non-cognate B cells relayed antigen opsonized by newly produced antibodies from the subcapsular sinus to the germinal center and affinity maturation was impaired when this transport process was disrupted. Thus, we characterize SCS macrophages as specialized antigen-presenting cells functioning at the apex of an antigen transport chain that promotes humoral immunity