Dataset Information

Impact of an Immune Modulator Mycobacterium-w on Adaptive Natural Killer Cells and Protection Against COVID-19.

ABSTRACT: The kinetics of NKG2C⁺ adaptive natural killer (ANK) cells and NKG2A⁺inhibitory NK (iNK) cells with respect to the incidence of SARS-CoV-2 infection were studied for 6 months in a cohort of healthcare workers following the administration of the heat-killed Mycobacterium w (Mw group) in comparison to a control group. In both groups, corona virus disease 2019 (COVID-19) correlated with lower NKG2C⁺ANK cells at baseline. There was a significant upregulation of NKG2C expression and IFN-γ release in the Mw group (p=0.0009), particularly in those with a lower baseline NKG2C expression, along with the downregulation of iNK cells (p<0.0001). This translated to a significant reduction in the incidence and severity of COVID-19 in the Mw group (incidence risk ratio-0.15, p=0.0004). RNA-seq analysis at 6 months showed an upregulation of the ANK pathway genes and an enhanced ANK-mediated antibody-dependent cellular cytotoxicity (ADCC) signature. Thus, Mw was observed to have a salutary impact on the ANK cell profile and a long-term upregulation of ANK-ADCC pathways, which could have provided protection against COVID-19 in a non-immune high-risk population.

SUBMITTER: Jaiswal SR

PROVIDER: S-EPMC9115578 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Impact of an Immune Modulator Mycobacterium-w on Adaptive Natural Killer Cells and Protection Against COVID-19.

Jaiswal Sarita Rani SR Arunachalam Jaganath J Saifullah Ashraf A Lakhchaura Rohit R Tailor Dhanir D Mehta Anupama A Bhagawati Gitali G Aiyer Hemamalini H Khamar Bakulesh B Malhotra Sanjay V SV Chakrabarti Suparno S

Frontiers in immunology 20220504

The kinetics of NKG2C+ adaptive natural killer (ANK) cells and NKG2A+inhibitory NK (iNK) cells with respect to the incidence of SARS-CoV-2 infection were studied for 6 months in a cohort of healthcare workers following the administration of the heat-killed Mycobacterium w (Mw group) in comparison to a control group. In both groups, corona virus disease 2019 (COVID-19) correlated with lower NKG2C+ANK cells at baseline. There was a significant upregulation o ...[more]

PMID: 35603154

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Project description:Whole transcriptome Differential Gene Expression (DGE) analysis was carried out on four biological replicates of both Mw (0.1 ml Mw administrated intradermally in each arm) and Control group at 6 months following exposure to Mycobacterium-w. Sequencing was done through Direct cDNA Sequencing (oxford nanopore technologies, Oxford, UK) using RNA isolated from Peripheral blood mononuclear cells (PBMC) by Trizol method. Native barcoding and adaptor ligation was done according to the manufacturer’s instructions. Ligated cDNA was loaded on the flow cell (R9.4.1) in MinION and were sequenced specifying 72 hours protocol. MinKNOW (v21.06.10, Microsoft Windows OS based) was used to generate FAST5 files. FAST5 files were base-called with CPU based Guppy basecaller (v.5.0.11) (ONT) to generate FASTQ files. DGE analysis was done using “pipeline-transcriptome-de” (https://github.com/nanoporetech/pipeline-transcriptome-de) pipeline. DGE analysis confirmed that upregulation of ANK pathway was evident at 6 months in the Mw group. Apart from upregulation of KLRC2 and B3GAT1 and downregulation of KLRC1, the key transcription factor in the ANK pathway, BCL11b, was persistently upregulated. Downregulation of EAT-2 and PLZF further corroborated the classic gene expression signature of ANK cells. Moreover, increased expression of AT-rich interaction domain 5B (ARID5B), as demonstrated in the Mw group plays an important role in enhanced metabolism in ANK cells as well as increased IFN-γ release and survival. DGE analysis also revealed an enhancement of ANK mediated ADCC pathway, with significant upregulation of CD247 along with downregulation of FCER1G, which is a typical signature of ANK-ADCC. Both CD247 and FCER1G are adapter molecules for FCGRIIIA (CD16) with CD247 possessing 3 ITAMs against one ITAM of FCER1G, increasing the ADCC several folds. It is possible that Mw induced augmentation of NK-ADCC might potentiate the efficacy of SARS-CoV2 vaccines as well.

Dataset Information

Impact of an Immune Modulator Mycobacterium-w on Adaptive Natural Killer Cells and Protection Against COVID-19.

Publications

Impact of an Immune Modulator Mycobacterium-w on Adaptive Natural Killer Cells and Protection Against COVID-19.

Similar Datasets

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