Protective Immunity to Mycobacterium tuberculosis Infection by Chemokine and Cytokine Conditioned CFP-10 Differentiated Dendritic Cells

BACKGROUND: Dendritic cells (DCs) play major roles in mediating immune responses to mycobacteria. A crucial aspect of this is the priming of T cells via chemokines and cytokines. In this study we investigated the roles of chemokines RANTES and IP-10 in regulating protective responses from Mycobacterium tuberculosis (M. tb) 10 kDa Culture Filtrate Protein-10 (CFP-10) differentiated DCs (CFP10-DCs). METHODS AND FINDINGS: Infection of CFP10-DCs with mycobacteria down-modulated RANTES and IP-10 levels. Pathway specific microarray analyses showed that in addition to RANTES and IP-10, mycobacteria infected CFP10-DCs showed reduced expression of many Th1 promoting chemokines and chemokine receptors. Importantly, T cells co-cultured with RANTES and IP-10 conditioned CFP10-DCs mediated killing of mycobacteria from infected macrophages. Similarly, T cells recruited by RANTES and IP-10 conditioned CFP10-DCs mediated significant killing of mycobacteria from infected macrophages. IFN-gamma treatment of CFP10-DCs restored RANTES and IP-10 levels and T cells activated by these DCs mediated significant killing of virulent M. tb inside macrophages. Adoptive transfer of either RANTES and IP-10 or IL-12 and IFN-gamma conditioned CFP10-DCs cleared an established M. tb infection in mice. The extent of clearance was similar to that obtained with drug treatment. CONCLUSIONS: These results indicate that chemokine and cytokine secretion by DCs differentiated by M. tb antigens such as CFP-10 play major roles in regulating protective immune responses at sites of infection

Housing price, financial development, energy intensity, FDI inflows: Global evidence

We examine the long-run and short-run impact of energy financial development, energy intensity and FDI inflows on housing prices by employing an international sample of 35 countries over the period 1980-2018. Using the two-step system GMM approach, unit root and cointegration tests, our empirical results imply strong cointegration and cross-dependence between housing price, energy intensity, financial development and economic growth. The regression results indicate the consistent outcomes; however, the magnitude and relation between housing price, energy intensity, and financial development are volatile when we control for different economic indicators through various econometric approaches. The results lend further empirical evidence on the transmission and response of housing prices to different economic factors

Platelet rich plasma enhances osteoconductive properties of a hydroxyapatite-β-tricalcium phosphate scaffold (Skelite™) for late healing of critical size rabbit calvarial defects

11siThe use of platelet rich plasma (PRP) in bone repair remains highly controversial. In this work, we evaluated the effect of lyophilized PRP on bone regeneration when associated with a silicon stabilized hydroxyapatite tricalcium phosphate scaffold in a rabbit calvarial defect (Skelite™). Critical defects were created in the calvaria of twenty-four rabbits. The periosteum was removed and the defects were either left empty or filled with allogeneic PRP gel; Skelite particles; Skelite and PRP gel. Four animals were killed after 4 weeks, 10 animals after 8 and 10 after 16 weeks. Specimens were processed for X-ray microtomography (μCT) and for resin embedded histology. μCT analysis revealed significant osteoid-like matrix and new bone deposition in PRP + Skelite group at both 8 and 16 weeks in respect to Skelite alone. Histologically, PRP + Skelite defects were highly cellular with more abundant osteoid deposition and more regular collagen fibres. Moreover, in vitro migration assays confirmed the chemotactic effect of PRP to endothelial and osteoprogenitor cells. We conclude that the addition of PRP influenced the local tissue microenvironment by providing key cryptic factors for regeneration, thereby enhancing progenitor cell recruitment, collagen and bone matrix deposition, and by creating a bridging interface between the scaffold and bone.nonenoneEl Backly, Rania M.; Zaky, Samer H.; Canciani, Barbara; Saad, Manal M.; Eweida, Ahmed M.; Brun, Francesco; Tromba, Giuliana; Komlev, Vladimir S.; Mastrogiacomo, Maddalena; Marei, Mona K.; Cancedda, RanieriEl Backly, Rania M.; Zaky, Samer H.; Canciani, Barbara; Saad, Manal M.; Eweida, Ahmed M.; Brun, Francesco; Tromba, Giuliana; Komlev, Vladimir S.; Mastrogiacomo, Maddalena; Marei, Mona K.; Cancedda, Ranier