Group A Streptococcal S Protein Utilizes Red Blood Cells as Immune Camouflage and Is a Critical Determinant for Immune Evasion.

Group A Streptococcus (GAS) is a human-specific pathogen that evades the host immune response through the elaboration of multiple virulence factors. Although many of these factors have been studied, numerous proteins encoded by the GAS genome are of unknown function. Herein, we characterize a biomimetic red blood cell (RBC)-captured protein of unknown function-annotated subsequently as S protein-in GAS pathophysiology. S protein maintains the hydrophobic properties of GAS, and its absence reduces survival in human blood. S protein facilitates GAS coating with lysed RBCs to promote molecular mimicry, which increases virulence in vitro and in vivo. Proteomic profiling reveals that the removal of S protein from GAS alters cellular and extracellular protein landscapes and is accompanied by a decrease in the abundance of several key GAS virulence determinants. In vivo, the absence of S protein results in a striking attenuation of virulence and promotes a robust immune response and immunological memory

Quantitative temporal in vivo proteomics (QTiPs) deciphers the transition of virus-driven myeloid cells into M2 macrophages

Myeloid cells play a central role in the context of viral eradication, yet precisely how these cells differentiate throughout the course of acute infections is poorly understood. In this study, we have developed a novel quantitative temporal in vivo proteomics (QTiPs) platform to capture proteomic signatures of temporally transitioning virus-driven myeloid cells directly in situ, thus taking into consideration host–virus interactions throughout the course of an infection. QTiPs, in combination with phenotypic, functional, and metabolic analyses, elucidated a pivotal role for inflammatory CD11b⁺, Ly6G‾, Ly6C^high-low cells in antiviral immune response and viral clearance. Most importantly, the time-resolved QTiPs data set showed the transition of CD11b⁺, Ly6G‾, Ly6C^high-low cells into M2-like macrophages, which displayed increased antigen-presentation capacities and bioenergetic demands late in infection. We elucidated the pivotal role of myeloid cells in virus clearance and show how these cells phenotypically, functionally, and metabolically undergo a timely transition from inflammatory to M2-like macrophages in vivo. With respect to the growing appreciation for in vivo examination of viral–host interactions and for the role of myeloid cells, this study elucidates the use of quantitative proteomics to reveal the role and response of distinct immune cell populations throughout the course of virus infection.This work was supported by grants from the Canadian Institutes of Health Research (CIHR) and Terry Fox Research Institute (TFRI) to S.G. and P.W.L. Authors D.R.C., Y.K., and T.S. are supported by the CIHR. J.P.M. and B.E.K. are supported through the Cancer Research Training Program (CRTP) of BHCRI. D.R.C. was supported previously by CRTP from BHCRI and the Nova Scotia Health Research Foundation (NSHRF). Nova Scotia Graduate Scholarships fund both N.H. and P.K. Work by J.A.P. was funded in part by NIH/NIDDK grant K01 DK098285. M.P.W. was supported by a Wellcome Trust Senior Fellowship (108070/Z/15/Z). We acknowledge Devanand Pinto and Ken Chisholm (National Research Council) as well as Alejandro Cohen at the Dalhousie Proteomics Core Facility and Derek Rowter and Renee Raudonis at Dalhousie Flow cytometry suites

Bystander TN cells_proteomics

10-plex proteomics analysis of different mouse CD8 T cell subsets- naive CD8 T cells, bystander activated naive CD8 T cells (1 dpi), bystander naive CD8 T cells (7 dpi) and effector memory T cells (7 dpi). The dataset aimed to characterize the molecular signatures and protein networks that drive the induction of bystander naive CD8 T cells after virus exposure.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Bystander TN_Metabolomics

Metabolomics analysis of bystander activated naive CD8 mouse T cells after virus exposure. In this dataset we aimed to characterize the metabolic signatures that drive the induction of bystander activated naive CD8 T cells when compared to naive CD8 T cells 1 day post exposure to virus.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Group A Streptococcal S Protein Utilizes Red Blood Cells as Immune Camouflage and Is a Critical Determinant for Immune Evasion.

Group A Streptococcus (GAS) is a human-specific pathogen that evades the host immune response through the elaboration of multiple virulence factors. Although many of these factors have been studied, numerous proteins encoded by the GAS genome are of unknown function. Herein, we characterize a biomimetic red blood cell (RBC)-captured protein of unknown function-annotated subsequently as S protein-in GAS pathophysiology. S protein maintains the hydrophobic properties of GAS, and its absence reduces survival in human blood. S protein facilitates GAS coating with lysed RBCs to promote molecular mimicry, which increases virulence in vitro and in vivo. Proteomic profiling reveals that the removal of S protein from GAS alters cellular and extracellular protein landscapes and is accompanied by a decrease in the abundance of several key GAS virulence determinants. In vivo, the absence of S protein results in a striking attenuation of virulence and promotes a robust immune response and immunological memory

AYUSH-64 as add-on to standard care in asymptomatic and mild cases of COVID-19: A randomized controlled trial

Background: The evidence on the efficacy and safety of Ayurveda interventions as add-on to the standard conventional care for COVID-19 is limited. This study was planned to explore the potential of AYUSH-64 as add-on to conventional care in improving the clinical recovery and negative RT-PCR conversion in asymptomatic and mild COVID-19 cases. Materials and Methods: An open-label randomized controlled study was conducted at Government Medical College, Nagpur, Maharashtra, India with a sample size of 60 participants. In this study, asymptomatic or mild COVID-19 patients were randomized and allocated into intervention and control group in 1:1 ratio. AYUSH-64 two capsules (500 mg each) were administered thrice daily, after food with water for 30 days along with standard care in the intervention group, while the control group received only standard care. The effect of the interventions was assessed in terms of negative RT-PCR for COVID-19, clinical cure rate and inflammatory cytokines. Outcome measures: Primary outcome was the time to attain negative RT-PCR for COVID-19 and proportion of participants turned RT-PCR negative for COVID-19 at 7th, 15th, 22nd and 30th day respectively in the intervention group compared to the control group. Secondary outcomes were the proportion of participants who attained clinical recovery at 7th, 15th, 22nd, and 30thday; improvement in laboratory parameters on the 30th day (as compared to baseline) and incidence of Adverse Drug Reactions/Adverse Events (ADRs/AEs). The data was compared within group using paired sample t-test/ Wilcoxon signed rank test and between group using independent sample t-test/Mann-Whitney test. Results: Statistically significant difference was not observed in the proportion of participants who turned RT-PCR negative during each of the follow-ups (p=0.134) and both groups demonstrated comparable efficacy. The clinical recovery rate in terms of time taken for complete cure of symptoms in the symptomatic participants was 60% and 37% on day 15 (p=0.098) and 100% and 85.2% on day 30 (p=0.112), in the intervention and control group respectively which is numerically a better clinical outcome in the intervention group. The improvement in the inflammatory markers such as IL-6, TNF-α and D-dimer was statistically significant in the intervention group (p<0.05). None of the participants developed any complications nor were any significant ADR/AE observed in both the groups. Conclusion: In patients with asymptomatic and mild COVID-19, AYUSH-64 as add-on to standard conventional care, contributed to improving the duration for attaining complete clinical cure and demonstrated potential in reducing the levels of pro-inflammatory markers in the body