In the healthy intestinal mucosa, homeostasis between the immune system and commensal microflora prevents detrimental inflammatory responses. Infection with acute enteropathogens such as Salmonella enterica serovar Typhimurium disturbs this homeostasis and triggers inflammation, but the underlying mechanisms are poorly understood. We found that bacterial delivery or ectopic expression of the S. Typhimurium type III effector protein SopE, a known activator of host cellular Rho GTPases, led to proinflammatory caspase-1 activation and consequent maturation and secretion of the cytokine IL-1beta. In vivo, SopE triggered mucosal inflammation in wild-type but not caspase-1(-/-), IL-1R(-/-), or IL-18(-/-) mice. Bone marrow chimeras indicated that caspase-1 was more important in stromal cells, most likely enterocytes, than in bone marrow-derived cells. SopE-mediated caspase-1 activation in vitro was mediated by cellular Rho GTPases Rac-1 and Cdc42. These findings implicate SopE-driven Rho GTPase-mediated caspase-1 activation in stromal cells as a mechanism eliciting mucosal inflammation during S. Typhimurium infection.

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Tumor progression is controlled by signals from cellular and extra-cellular microenvironment including stromal cells and the extracellular matrix. Consequently, three-dimensional in vitro tumor models are essential to study the interaction of tumor cells with their microenvironment appropriately in a biologically relevant manner. We have previously used organotypic co-cultures to analyze the malignant growth of human squamous cell carcinoma (SCC) cell lines on a stromal equivalent in vitro. In this model, SCC cell lines are grown on a collagen-I gel containing fibroblasts. Since macrophages play a critical role in the progression of many tumor types, we now have expanded this model by integrating macrophages into the collagen gel of these organotypic tumor co-cultures. This model was established as a murine and a human system of skin SCCs. The effect of macrophages on tumor progression depends on their polarization. We demonstrate that macrophage polarization in organotypic co-cultures can be modulated towards and M1 or an M2 phenotype by adding recombinant IFN-γ and LPS or IL-4 respectively to the growth medium. IL-4 stimulation of macrophage-containing cultures resulted in enhanced tumor cell invasion evidenced by degradation of the basement membrane, enhanced collagenolytic activity and increased MMP-2 and MMP-9. Interestingly, extended co-culture with tumor cells for three weeks resulted in spontaneous M2 polarization of macrophages without IL-4 treatment. Thus, we demonstrate that macrophages can be successfully integrated into organotypic co-cultures of murine or human skin SCCs and that this model can be exploited to analyze macrophage activation towards a tumor supporting phenotype.

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Highly porous carbide-derived carbon (CDC) mesofoams (DUT-70) are prepared by nanocasting of mesocellular silica foams with a polycarbosilane precursor. Ceramic conversion followed by silica removal and high-temperature chlorine treatment yields CDCs with a hierarchical micro-mesopore arrangement. This new type of polymer-based CDC is characterized by specifi c surface areas as high as 2700 m 2 g −1 , coupled with ultrahigh microand mesopore volumes up to 2.6 cm 3 g −1 . The relationship between synthesis conditions and the properties of the resulting carbon materials is described in detail, allowing precise control of the properties of DUT-70. Since the hierarchical pore system ensures both effi cient mass transfer and high capacities, the novel CDC shows outstanding performance as an electrode material in electrochemical double-layer capacitors (EDLCs) with specifi c capacities above 240 F g −1 when measured in a symmetrical two-electrode confi guration. Remarkable capacities of 175 F g −1 can be retained even at high current densities of 20 A g −1 as a result of the enhanced ion-transport pathways provided by the cellular mesostructure. Moreover, DUT-70 can be infi ltrated with sulfur and host the active material in lithium-sulfur battery cathodes. Reversible capacities of 790 mAh g −1 are achieved at a current rate of C/10 after 100 cycles, which renders DUT-70 an ideal support material for electrochemical energy-storage applications.