Numerous DC-based vaccine strategies have emerged as new immunotherapeutics[3, 4, 65]: nanoparticles delivering specific antigen in vivo to DCs[66]; DCs programmed in vivo by cytokines released from an implant biomaterial scaffold[14]; or by in vivo pre-injection of cytokines.[67] Interestingly, when DCs are pre-treated

with glucocorticoids (dexamethasone) in vitro, the endocytic capacity and the expression selleck compound levels of receptors for endocytosis after DC maturation by TNF-α, remained higher than control DCs (no dexamethasone), but CD86 expression was suppressed before and after TNF-α stimulation.[34] Certainly, chemokine programming of DCs appears a feasible way to directly or indirectly control adaptive immunity. To further confirm the multifunctional impacts

of chemokine programming, we are currently quantifying the interaction of the programmed primary bone marrow-derived DCs and T cells. We demonstrate here that two different chemokines, each of which is selectively recognized by iDCs or mDCs, have a synergistic impact on programming DCs to retain their endocytic capacity, even after DC maturation. Further, we show that this programming induces multifunctional effects on the DC phenotype. These results suggest that DC-based vaccine Src inhibitor strategies could be modified by overcoming the natural limit (significant reduction of antigen uptake and processing upon DC maturation) of the host immune response. For instance, ex vivo transfection of DCs can be enhanced by chemokine containing medium, whereas in vivo programming of DCs could be possible using implanted biomaterials releasing chemokines and antigen sequentially or chemokine/antigen targeting iDCs residing in lymphoid organs.[68] In this way, even though iDCs may be accidently pre-matured by an adjuvant before internalizing antigens, they would still retain their endocytic capacity at a certain level, which would increase the overall vaccine GBA3 efficiency. This

work was generously supported by the National Institutes of Health: NIAID R01AI074661 and NIDCR R01DE018701. The authors declare no competing interests. “
“A better understanding of the genotypic and phenotypic adaptation of sessile (biofilm-associated) microorganisms to various forms of stress is required in order to develop more effective antibiofilm strategies. This review presents an overview of what high-throughput transcriptomic analyses have taught us concerning the response of various clinically relevant microorganisms (including Pseudomonas aeruginosa, Burkholderia cenocepacia and Candida albicans) to treatment with antibiotics or disinfectants.