Biology subjects

Hassan, J.

Publications and source records attributed to Hassan, J..

3 recordsLinked to original sources

bioRxiv2022

Temporal profiling of CD4 T-cell activation and differentiation upon SARS-CoV-2 spike protein immunisation

CD4 T-cells require T-cell receptor (TCR) signalling for their activation and differentiation. Foxp3+ regulatory T-cells (Treg) are dependent on TCR signals for their differentiation and suppressive function. However, it is not fully known how TCR signalling controls the differentiation of polyclonal CD4 T-cells upon antigen recognition at the single-cell level in vivo. In this study, using Nr4a3-Tocky (Timer-of-cell-kinetics-and-activity), which analyses temporal changes of antigen-reactive T-cells following TCR signalling, we investigated T-cell response to Spike protein fragments (S1a, S1b, S2a, and S2b) upon immunisation. We show that S1a and S2a induced the differentiation of PD1hiCXCR5+ T follicular helper (Tfh) cells, which is related to CD4 T-cell immunogenicity. In contrast, S1b induced CD25hiGITRhiPD-1int Treg, which intermittently received TCR signalling. Using Foxp3-Tocky, which analyses Foxp3 transcriptional dynamics, the S1b-reactive Treg sustained Foxp3 transcription over time, which is a hallmark of activated Treg. Foxp3 fate-mapping showed that the S1b-reactive Treg were derived not from pre-existing thymic Treg, suggesting Foxp3 induction in non-Treg cells. Thus, the current study reveals temporally dynamic differentiation of CD4 T-cells and Treg upon immunisation in the polyclonal TCR repertoire.

immunology↗

bioRxiv2022

Single-cell level temporal profiling of tumour-reactive T cells under immune checkpoint blockade

The blockade of the immune checkpoints PD-1 and CTLA-4 enhances T cell response. However, it is largely unknown how antigen-reactive T cells regulate their checkpoint expression in vivo and whether and how the checkpoint blockade can change activation dynamics of tumour-reactive T cells. To address this, here we used Nr4a3-Timer-of-cell-kinetics-and-activity (Tocky), which allows analysis of temporal changes of activated T cells following TCR signalling in vivo. By analysing melanoma-bearing Nr4a3 Tocky mice, we elucidate hidden dynamics of tumour-reactive T cells in the steady-state. Checkpoint blockade depleted highly activated effector Treg, while promoting unique effector T cell populations, and thus differentially modulating activation of tumour-reactive T cell populations. Furthermore, multidimensional analysis and seamless analysis of Tocky and scRNA-seq revealed a full spectrum of T cell dynamics in response to tumour burden and treatment with checkpoint blockade. Lastly, we propose a rational design of combinatorial therapy to further enhance T cell activities.

immunology↗

bioRxiv2022

Genomic characteristics, virulence and antimicrobial resistance in avian pathogenic Escherichia coli MTR_BAU02 strain isolated from layer farms in Bangladesh

BackgroundColibacillosis, caused by avian pathogenic Escherichia coli (APEC), is one of the most significant infectious diseases affecting poultry worldwide. APEC is one of the leading causes of mortality and morbidity associated with significant economic losses in the poultry industry. ObjectiveThis study was aimed to determine the genomic diversity, virulence factor genes (VFGs) and antimicrobial resistance (AMR) genes in the APEC isolated from layer chickens using whole-genome sequencing (WGS). MethodAPEC MTR_BAU02 strain was isolated from the sick and dead birds. Genomic DNA from APEC MTR_BAU02 strain was extracted using commercial DNA extraction kit, WGS libraries were prepared using the Nextera DNA Flex Library Prep Kit, and finally, paired-end (2 x 250) WGS performed using Illumina MiSeq sequencer. ResultsThe genome size of strain APEC MTR_BAU02 is 4,924,680 bp with a GC content of 51.1% and 4,681 protein-coding sequences. Among the annotated WGS reads, 99.71% reads mapped to Enterobacteriaceae genomes. Based on the phylogenetic analysis of the APEC MTR_BAU02 genome and 99 reference genomes of E. coli, the APEC MTR_BAU02 genome showed sequence similarities with enterotoxigenic E. coli strains isolated from infections of different clinical severity. Metabolic functional annotations detected 380 SEED subsystems including genes coding for carbohydrate metabolism (17.34%), amino acid and derivatives (14.20%), protein metabolism (10.64%), cofactors, vitamins, prosthetic groups and pigments (7.49%), respiration (4.72%), membrane transport (4.49%), stress response (4.47%), motility and chemotaxis (4.46%), and virulence, disease and defense (2.22%). We also detected 92 VFGs and 122 AMR genes in the APEC MTR_BAU02 strain. ConclusionAssessment of these genomic features with functional genomic validation in commonly occurring serogroups of APEC will increase our understanding of the molecular pathogenesis, pave the way to early diagnosis and more effective control of colibacillosis, and improved animal welfare.

genomics↗