The role of nucleic acid sensors and type I IFNs in patient populations and animal models of autoinflammation.
The role of nucleic acid sensors and type I IFNs in patient populations and animal models of autoinflammation. Curr Opin Immunol. 2019 Sep 27;61:74-79 Authors: Nündel K, Marshak-Rothstein A Abstract A spectrum of human autoinflammatory conditions result from defects in cytosolic nucleic acid clearance or overexpression of the nucleic acid sensor STING. These patients often develop severely debilitating lesions and invariably show robust IFN signatures that have been attributed to the cGAS/STING signaling cascade and type I IFN. However, murine models that recapitulate major features of these syndromes have now shown that autoinflammation is more likely to depend on type II IFN/IFNgamma or type III IFN/IFNlambda, and further revealed a critical role for Th1 cells in tissue damage and the persistence of inflammation. These studies provide important insights about the types of IFNs, and the interplay of the innate and adaptive immune systems mediated by these IFNs, that can initiate and maintain the corresponding human diseases. They further point to type II/III IFNs and effector T cells as targets for more effective therapeutic strategies in the treatment of these patient populations. PMID: 31569013 [PubMed - as supplied by publisher]
This previously unknown mechanism for spotting foreign genetic material in the cytoplasm launches antiviral defenses even when the well-known immune mediator STING is absent.
ConclusionOur findings significantly contributes in the policy making at the administrative level including district level, state level and eventually to the nation.
Graft-versus-host disease (GVHD) remains a significant cause of morbidity and mortality in patients receiving allogeneic hematopoietic stem cell transplants (aHSCTs). Pre-HSCT chemoradiation results in the death of dividing cells and release of endogenous danger signals. These molecules drive the activation of antigen presenting cells (APCs) and the differentiation of allo-reactive donor T cells. We identified a role for Stimulator of Interferon Genes (STING), an innate immune sensor, in GVHD using pre-clinical MHC-matched unrelated donor (MUD) HSCT models.
This study also revealed that SV40 LT does indeed inhibit cGAS-STING interferon induction, but through a mechanism distinct from other DNA virus oncogenes. Collectively, these results indicate that while SV40 LT can inhibit cGAS-STING interferon induction, it does so in an unanticipated manner.
O'Kane GM, Wilson JM, Knox JJ, Connor A, Wang Y, Zogopoulos G, Gallinger S Abstract PURPOSE: The molecular drivers of antitumor immunity in pancreatic ductal adenocarcinoma (PDAC) are poorly understood, posing a major obstacle for the identification of patients potentially amenable for immune checkpoint blockade or other novel strategies. Here, we explore the association of chemokine expression with effector T cell infiltration in PDAC. EXPERIMENTAL DESIGN: Discovery cohorts comprised 113 primary resected PDAC and 107 PDAC liver metastases. Validation cohorts comprised 182 PDAC from TCGA and 92 PDACs from the...
In this study combination of immuno-informatics and molecular docking approach was used to constitute a MEBP vaccine. The ZIKV proteome was used for prediction of B-cell, T-cell (HTL &CTL) and IFN-γ epitopes. After prediction, highly antigenic and overlapping epitopes have been shortlisted which includes 14 CTL and 11 HTL epitopes that have been linked to the final peptide through AAY and GPGPG linkers respectively. An adjuvant at the N-end of the vaccine was added to improve the immunogenicity of the vaccine through the EAAAK linker. The final construct constitutes 435 amino acids after the addition of linkers a...
Typhus is a rare bacterial infection that people can acquire from insect bites. Discover its symptoms, risk factors, and the treatment options available.
This case report describes a woman in her 30s with a jellyfish sting on her right wrist, which caused erythematous serpiginous plaques with superficial scaling in a braceletlike shape.
Abstract During DNA virus infections, detection of cytosolic DNA by the cGAS-STING pathway leads to activation of IFN-β. Kaposi's Sarcoma Herpesvirus (KSHV), an oncogenic DNA virus, is the etiological agent of Kaposi's Sarcoma, an endothelial cell (EC)-based tumor. To investigate the role of STING during KSHV infection of primary ECs we identified a primary lymphatic EC sample that is defective for STING activation and we also knocked out STING in blood ECs. Ablation of STING in EC does not increase susceptibility to KSHV latent infection nor does it increase KSHV spread after lytic reactivation indicating ST...