Spatial and Temporal Control of Immune Cell Activation

The innate control of adaptive immunity has been the target of various therapeutics. By the chemical modification of the chemical patterns recognized by the Toll-like receptors (TLRs) on innate immune cells, we can further control the systemic immune response. Chemical modifications can be used to control the spatial presentation of multiple TLR agonists by covalent conjugation of two TLR agonists which serve as a synthetic mimic of macromolecular pathogens. Additionally, photocaging of TLR agonists is used to control the spatial and temporal presentation of agonists. These strategies would further provide mechanistic insight in TLR synergy as well as therapeutic insight in modulating the immune response

Spatial and Temporal Control of Immune Cell Activation

The innate control of adaptive immunity has been the target of various therapeutics. By the chemical modification of the chemical patterns recognized by the Toll-like receptors (TLRs) on innate immune cells, we can further control the systemic immune response. Chemical modifications can be used to control the spatial presentation of multiple TLR agonists by covalent conjugation of two TLR agonists which serve as a synthetic mimic of macromolecular pathogens. Additionally, photocaging of TLR agonists is used to control the spatial and temporal presentation of agonists. These strategies would further provide mechanistic insight in TLR synergy as well as therapeutic insight in modulating the immune response

Association between Fibrinogen-to-Albumin Ratio and Prognosis in Patients Admitted to an Intensive Care Unit

The objective of this study was to investigate the usefulness of fibrinogen-to-albumin ratio (FAR) as a prognostic marker in patients admitted to an intensive care unit (ICU) compared with Sequential Organ Failure Assessment (SOFA) score, a widely used prognostic scoring system. An inverse probability weighting (IPW) was used to control for selection bias and confounding factors. After IPW adjustment, the high FAR group showed significantly higher risk of 1-year compared with low FAR group (36.4% vs. 12.4%, adjust hazard ratio = 1.72; 95% confidence interval (CI): 1.59–1.86; p p = 0.532). In this study, FAR and SOFA score at ICU admission were associated with 1-year mortality in patients admitted to an ICU. Especially, FAR was easier to obtain in critically ill patients than SOFA score. Therefore, FAR is feasible and might help predict long-term mortality in these patients

Immune Response Modulation of Conjugated Agonists with Changing Linker Length

We report immune response modulation with linked Toll-like receptor (TLR) agonists. Conjugating two agonists of synergistic TLRs induce an increase in immune activity compared to equal molarity of soluble agonists. Additionally, varying the distance between the agonists by changing the linker length alters the level of macrophage NF-κB activity as well as primary bone marrow derived dendritic cell IL-6 production. This modulation is effected by the size of the agonists and the pairing of the stimulated TLRs. The sensitivity of linker-length-dependent immune activity of conjugated agonists provides the potential for developing application specific therapeutics

Light Guided In-vivo Activation of Innate Immune Cells with Photocaged TLR 2/6 Agonist

The complexity of the immune system creates challenges in exploring its importance and robustness. To date, there have been few techniques developed to manipulate individual components of the immune system in an in vivo environment. Here we show a light-based dendritic cell (DC) activation allowing spatial and temporal control of immune activation in vivo. Additionally, we show time dependent changes in RNA profiles of the draining lymph node, suggesting a change in cell profile following DC migration and indicating that the cells migrating have been activated towards antigen presentation