Streptococcus pneumoniae is a major cause of pneumonia in infants and the elderly. Innate defenses are essential to the control of pneumococcal infections, and deficient responses can trigger disease in susceptible individuals. Here we showed that flagellin can locally activate innate immunity and thereby increase the resistance to acute pneumonia. Flagellin mucosal treatment improved S. pneumoniae clearance in the lungs and promoted increased survival of infection. In addition, lung architecture was fully restored after the treatment of infected mice, indicating that flagellin allows the reestablishment of steady-state conditions. Using a flagellin mutant that is unable to signal through Toll-like receptor 5 (TLR5), we established that TLR5 signaling is essential for protection. In the respiratory tract, flagellin induced neutrophil infiltration into airways and upregulated the expression of genes coding for interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-␣), CXCL1, CXCL2, and CCL20. Using depleting antibodies, we demonstrated that neutrophils are major effectors of protection. Further, we found that B-and T-cell-deficient SCID mice clear S. pneumoniae challenge to the same extent as immunocompetent animals, suggesting that these cell populations are not required for flagellin-induced protection. In conclusion, this study emphasizes that mucosal stimulation of innate immunity by a TLR not naturally engaged by S. pneumoniae can increase the potential to cure pneumococcal pneumonia.

SummaryDespite the efficacy of current immune-chemotherapy for treatment of Bcell non-Hodgkin lymphoma, a substantial proportion of patients relapse, highlighting the need for new therapeutic modalities. The use of live microorganisms to develop anti-tumoural therapies has evolved since Coley's toxin and is now receiving renewed attention. Salmonella Typhimurium has been shown to be highly effective as an anti-tumour agent in many solid cancer models, but it has not been used in haematooncology. Here, we report that intra-tumoural administration of LVR01 (attenuated S. Typhimurium strain with safety profile) elicits local and systemic anti-tumour immunity, resulting in extended survival in a lymphoma model. LVR01 induces intra-tumoural recruitment of neutrophils and activated CD8 + T cells, as well as increasing the natural killer cell activation status. Furthermore, a systemic specific anti-tumour response with a clear T helper type 1 profile was observed. This approach is an alternative therapeutic strategy for lymphoma patients that could be easily moved into clinical trials.

No abstract

The establishment of Leishmania infection in mammalian hosts and the subsequent manifestation of clinical symptoms require internalization into macrophages, immune evasion and parasite survival and replication. Although many of the genes involved in these processes have been described, the genetic and genomic variability associated to differences in virulence is largely unknown. Here we present the genomic variation of four Leishmania (Viannia) panamensis strains exhibiting different levels of virulence in BALB/c mice and its application to predict novel genes related to virulence. De novo DNA sequencing and assembly of the most virulent strain allowed comparative genomics analysis with sequenced L. (Viannia) panamensis and L. (Viannia) braziliensis strains, and showed important variations at intra and interspecific levels. Moreover, the mutation detection and a CNV search revealed both base and structural genomic variation within the species. Interestingly, we found differences in the copy number and protein diversity of some genes previously related to virulence. Several machine-learning approaches were applied to combine previous knowledge with features derived from genomic variation and predict a curated set of 66 novel genes related to virulence. These genes can be prioritized for validation experiments and could potentially become promising drug and immune targets for the development of novel prophylactic and therapeutic interventions.

Experiments were conducted to evaluate the rate of water vaporisation and the consequent permeability reduction caused by the flow of dry gas through porous media. Two sets of porous media were studied: unconsolidated Ottawa sandpacks and consolidated Berea cores, as well as various salinity brines ranging from 0 to 150 g/litre of NaCl. The experiments were conducted at an initial water saturation of about 14% for sandpacks and 24.6% for Berea cores. Tests indicate that the rate of water vaporisation increases with gas flow rate and decreases with salinity. The vaporisation of water from the porous media can result in halite drop-out. This might cause a reduction in the permeability of the porous media. The experiments showed that the reduction in permeability for sandpacks ranged from 0% for the lowest salinity to around 21% for the highest salinity used. In consolidated Berea cores this reduction ranged from 9% to 53% for the lowest and highest salinity respectively. Introduction The flow of dry gas through porous media vaporises water in order to fulfil the thermodynamic requirements at a given pressure, temperature and salinity of the brine saturating the rock. Also, the development of an increasing number of high- pressure, high-temperature (HT/HP) fields has arisen important issues concerning inorganic deposition in these systems given their frequently high salinity brines. As the pressure declines at constant temperature, water is vaporised given the increase of the molar water content in the gaseous phase. This produces an over-concentration of dissolved salts and the solubility limit can be reached with the subsequent salt precipitation. Several authors have reported field cases where precipitation of NaCl is believed to be the cause of formation damage and it has been usually associated to water vaporisation1,2,3,4. Background Dodson and Standing5 reported experimental studies in PVT cells to determine the solubility of a natural gas (?=0,655) in brine and to determine the solubility of water vapor in natural gas. The experiments were performed at pressures ranging from 500 to 5000 psia, temperatures from 100 to 250°F and brines having up to 25000 ppm of total solids. It was found that the amount of water in the gas phase increases with temperature and decreases with pressure and solids content. Place and Smith1 reported a severe decline in productivity for the well Shell Ridgway 1-R in the Southwest Pineywoods Field, MS. After observation of the decrease in Cl-/K+ and Cl-/Li+ ratios in the produced fluids, the authors concluded that the deposition of NaCl at the open hole was responsible for the significant loss of productivity. Even though the water saturation in the main pays was considered to be inmmobile (15% to 26%), the overlying and isolated zones had water saturations in the range of 35% to 50%. Under this scenario, the flowing gas would evaporate water from the main pays increasing the concentration of the brine. Also, if less concentrated brine is flowing into the wellbore from the high saturation zones, the gas would evaporate this less concentrated brine with the subsequent NaCl deposition. The author's point out that only when the salinity of the pay zones exceeds that of the overlying high saturation zones the episode of salt deposition and plugging will be initiated. Morin and Montel3 studied the dehydration process in order to predict the conditions for precipitation of NaCl in the tubing. The authors mention three situations that contribute to the vaporisation process including the flow of gas from layers at different water saturation, important pressure drop with small temperature decrease and the increase in vaporisation when the gas flows from the near wellbore area to the well. The latter situation appears because the porous media causes a decrease in the water content of gas compared to the value outside of it given that capillarity and adsorption tend to retain the water in the rock. The authors remark the influence of water saturation on the rate of water vaporisation.

SUMMARYInfection by larvalEchinococcus granulosusis usually characterized by tight inflammatory control. However, various degrees of chronic granulomatous inflammation are also observed, reaching a high point in infection of cattle by the most prevalent parasite strain worldwide, which is not well adapted to this host species. In this context, epithelioid and multinucleated giant macrophages surround the parasite, and the secreted products of these cells often associate with the larval wall. The phagocyte-specific S100 proteins, S100A8, S100A9 and S100A12, are important non-conventionally secreted amplifiers of inflammatory responses. We have analysed by proteomics and immunohistochemistry the presence of these proteins at theE. granulosuslarva-host interface. We found that, in the context of inflammatory control as observed in human infections, the S100 proteins are not abundant, but S100A9 and S100A8 can be expressed by eosinophils distal to the parasite. In the granulomatous inflammation context as observed in cattle infections, we found that S100A12 is one of the most abundant host-derived, parasite-associated proteins, while S100A9 and S100A8 are not present at similarly high levels. As expected, S100A12 derives mostly from the epithelioid and multinucleated giant cells. S100A12, as well as cathepsin K and matrix metalloproteinase-9, also expressed byE. granulosus-elicited epithelioid cells, are connected to the Th17 arm of immunity, which may therefore be involved in this granulomatous response.

Rotavirus infection has been reported to induce an inflammatory response in the host cell accompanied by the increased expression or activation of some cellular molecules including ROS, NF-κB, and COX-2. PPARγ stimulation and N-acetylcysteine (NAC) treatment have been found to interfere with viral infections including rotavirus infection. Small intestinal villi isolated from in vivo infected mice with rotavirus ECwt were analyzed for the percentage of ECwt-infected cells, the presence of rotavirus antigens, and infectious virion yield following treatment with pioglitazone. Isolated villi were also infected in vitro and treated with PPARγ agonists (PGZ, TZD, RGZ, DHA, and ALA), all-trans retinoic acid (ATRA), and NAC. After treatments, the expression of cellular proteins including PPARγ, NF-κB, PDI, Hsc70, and COX-2 was analyzed using immunochemistry, ELISA, immunofluorescence, and Western blotting. The results showed that rotavirus infection led to an increased accumulation of the cellular proteins studied and ROS. The virus infection-induced accumulation of the cellular proteins studied and ROS was reduced upon pioglitazone treatment, causing also a concomitant reduction of the infectious virion yield. We hypothesized that rotavirus infection is benefiting from the induction of a host cell proinflammatory response and that the interference of the inflammatory pathways involved leads to decreased infection.

Histochemical stainings continue to be the gold standard in the diagnosis of intestinal dysganglionosis. The combination of two histochemical staining techniques provides a high level of accuracy in the diagnosis of intestinal dysganglionosis.