The trans-Golgi SNARE syntaxin 6 is recruited to the chlamydial inclusion membrane

Chlamydia trachomatis is an obligate intracellular pathogen that replicates within a parasitophorous vacuole termed an inclusion. The chlamydial inclusion is isolated from the endocytic pathway but fusogenic with Golgi-derived exocytic vesicles containing sphingomyelin and cholesterol. Sphingolipids are incorporated into the chlamydial cell wall and are considered essential for chlamydial development and viability. The mechanisms by which chlamydiae obtain eukaryotic lipids are poorly understood but require chlamydial protein synthesis and presumably modification of the inclusion membrane to initiate this interaction. A polarized cell model of chlamydial infection has demonstrated that chlamydiae preferentially intercept basolaterally directed, sphingomyelin-containing exocytic vesicles. Here we examine the localization and potential function of trans-Golgi and/or basolaterally associated soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in chlamydia-infected cells. The trans-Golgi SNARE protein syntaxin 6 is recruited to the chlamydial inclusion in a manner that requires chlamydial protein synthesis and is conserved among all chlamydial species examined. The localization of syntaxin 6 to the chlamydial inclusion requires a tyrosine motif or plasma membrane retrieval signal (YGRL). Thus in addition to expression of at least two inclusion membrane proteins that contain SNARE-like motifs, chlamydiae also actively recruit eukaryotic SNARE-family proteins

Endoplasmic Reticulum Stress Pathway-Mediated Apoptosis in Macrophages Contributes to the Survival of Mycobacterium tuberculosis

BACKGROUND: Apoptosis is thought to play a role in host defenses against intracellular pathogens, including Mycobacterium tuberculosis (Mtb), by preventing the release of intracellular components and the spread of mycobacterial infection. This study aims to investigate the role of endoplasmic reticulum (ER) stress mediated apoptosis in mycobacteria infected macrophages. METHODOLOGY/PRINCIPAL FINDINGS: Here, we demonstrate that ER stress-induced apoptosis is associated with Mtb H37Rv-induced cell death of Raw264.7 murine macrophages. We have shown that Mtb H37Rv induced apoptosis are involved in activation of caspase-12, which resides on the cytoplasmic district of the ER. Mtb infection increase levels of other ER stress indicators in a time-dependent manner. Phosphorylation of eIF2α was decreased gradually after Mtb H37Rv infection signifying that Mtb H37Rv infection may affect eIF2α phosphorylation in an attempt to survive within macrophages. Interestingly, the survival of mycobacteria in macrophages was enhanced by silencing CHOP expression. In contrast, survival rate of mycobacteria was reduced by phosphorylation of the eIF2α. Futhermore, the levels of ROS, NO or CHOP expression were significantly increased by live Mtb H37Rv compared to heat-killed Mtb H37Rv indicating that live Mtb H37Rv could induce ER stress response. CONCLUSION/SIGNIFICANCE: These findings indicate that eIF2α/CHOP pathway may influence intracellular survival of Mtb H37Rv in macrophages and only live Mtb H37Rv can induce ER stress response. The data support the ER stress pathway plays an important role in the pathogenesis and persistence of mycobacteria

Efficient Capture of Infected Neutrophils by Dendritic Cells in the Skin Inhibits the Early Anti-Leishmania Response

Neutrophils and dendritic cells (DCs) converge at localized sites of acute inflammation in the skin following pathogen deposition by the bites of arthropod vectors or by needle injection. Prior studies in mice have shown that neutrophils are the predominant recruited and infected cells during the earliest stage of Leishmania major infection in the skin, and that neutrophil depletion promotes host resistance to sand fly transmitted infection. How the massive influx of neutrophils aimed at wound repair and sterilization might modulate the function of DCs in the skin has not been previously addressed. The infected neutrophils recovered from the skin expressed elevated apoptotic markers compared to uninfected neutrophils, and were preferentially captured by dermal DCs when injected back into the mouse ear dermis. Following challenge with L. major directly, the majority of the infected DCs recovered from the skin at 24 hr stained positive for neutrophil markers, indicating that they acquired their parasites via uptake of infected neutrophils. When infected, dermal DCs were recovered from neutrophil depleted mice, their expression of activation markers was markedly enhanced, as was their capacity to present Leishmania antigens ex vivo. Neutrophil depletion also enhanced the priming of L. major specific CD4+ T cells in vivo. The findings suggest that following their rapid uptake by neutrophils in the skin, L. major exploits the immunosuppressive effects associated with the apoptotic cell clearance function of DCs to inhibit the development of acquired resistance until the acute neutrophilic response is resolved

The forager societies on both sides of Baltic see : A comparative contextual and relational analysis

A comparative contextual and relational analysis of mortuary patterning, demographic structure, and regional interaction was performed in order to elucidate the similarities and differences of the forager societies on both sides of Baltic sea. Four hunter-fisher-gatherers complexes were selected by literature review: Skateholm in south coastline and Motala in the middle of Sweden, Oleni´ostrov in north Russia and Zvejnieki in Latvia. These Mesolithic complexes excavated and dated to 9500-6000 years before present. The analyses suggest that the society which produced those four forager organizations on both sides of Baltic sea were internally differentiated with a complex system of social differentiation that include hereditary social positions and economic ranking. This study suggested at the Oleni´ostrov and Zvejnieki Mesolithic population was partly mobile, and the sites were the places to bury the dead while in Skateholm the inhabitants were continuously stayed in the same geographical site. The positioning of the deceased in the grave as well as the composition of the grave goods adjusted to settlement societies. The results indicated to a general horizontal development of the societies with equality between different social categories in the Skateholm, Oleni´ostrov and Zvejnieki.  The unique site of Kanaljorden in Motala challenges our understanding of foragers societies, demographic structure and handling of the dead during the Eurasian Mesolithic.  The site has revealed disarticulated human crania intentionally placed at the bottom of a former lake. The adult crania exhibited antemortem blunt force trauma patterns differentiated by sex that were probably the result of interpersonal violence. The remains of wooden stakes were recovered inside two crania, indicating that they had been mounted. Taphonomic factors suggest that human bodies were manipulated prior to deposition

The forager societies on both sides of Baltic see : A comparative contextual and relational analysis

A comparative contextual and relational analysis of mortuary patterning, demographic structure, and regional interaction was performed in order to elucidate the similarities and differences of the forager societies on both sides of Baltic sea. Four hunter-fisher-gatherers complexes were selected by literature review: Skateholm in south coastline and Motala in the middle of Sweden, Oleni´ostrov in north Russia and Zvejnieki in Latvia. These Mesolithic complexes excavated and dated to 9500-6000 years before present. The analyses suggest that the society which produced those four forager organizations on both sides of Baltic sea were internally differentiated with a complex system of social differentiation that include hereditary social positions and economic ranking. This study suggested at the Oleni´ostrov and Zvejnieki Mesolithic population was partly mobile, and the sites were the places to bury the dead while in Skateholm the inhabitants were continuously stayed in the same geographical site. The positioning of the deceased in the grave as well as the composition of the grave goods adjusted to settlement societies. The results indicated to a general horizontal development of the societies with equality between different social categories in the Skateholm, Oleni´ostrov and Zvejnieki.  The unique site of Kanaljorden in Motala challenges our understanding of foragers societies, demographic structure and handling of the dead during the Eurasian Mesolithic.  The site has revealed disarticulated human crania intentionally placed at the bottom of a former lake. The adult crania exhibited antemortem blunt force trauma patterns differentiated by sex that were probably the result of interpersonal violence. The remains of wooden stakes were recovered inside two crania, indicating that they had been mounted. Taphonomic factors suggest that human bodies were manipulated prior to deposition