OAS1, OAS2 and OAS3 restrict intracellular M. tb replication and enhance cytokine secretion

The 2′,5′ (OASs) are known as mediators of the antiviral response system through activation of the RNA cleavage pathway. Interestingly, we observe OAS1, OAS2 and OAS3 upregulation in a number of gene expression signatures which discriminate active TB from latent TB infection, however their biologica...

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Main Authors: Gina Leisching, Victoria Cole, Aus T. Ali, Bienyameen Baker
Format: Article
Language:English
Published: Elsevier 2019-03-01
Series:International Journal of Infectious Diseases
Online Access:http://www.sciencedirect.com/science/article/pii/S1201971219300931
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author Gina Leisching
Victoria Cole
Aus T. Ali
Bienyameen Baker
author_facet Gina Leisching
Victoria Cole
Aus T. Ali
Bienyameen Baker
author_sort Gina Leisching
collection DOAJ
description The 2′,5′ (OASs) are known as mediators of the antiviral response system through activation of the RNA cleavage pathway. Interestingly, we observe OAS1, OAS2 and OAS3 upregulation in a number of gene expression signatures which discriminate active TB from latent TB infection, however their biological role during bacterial infection has not yet been elucidated. We observed that the expression of these genes was associated with pathogenicity and virulence of mycobacteria as infection with Mycobacterium bovis BCG failed to significantly induce OAS expression. Further, we observed that after silencing of these genes, M. tb CFU counts increased significantly 96 h post-infection in comparison to the respective controls. Luminex revealed that OAS silencing significantly decreased IL-1β, TNF-α and MCP-1 and had no effect of IL-10 secretion. We show for the first time that OAS1, 2 and 3 restrict intracellular pathogenic mycobacterial replication and enhance pro-inflammatory cytokine secretion. Keywords: M. tuberculosis, OAS, Host-defence, Anti-microbial, Pathogenesis, Virulence
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spelling doaj.art-df7b33037a16485f8055dc2e7e4554432022-12-22T02:09:03ZengElsevierInternational Journal of Infectious Diseases1201-97122019-03-0180S77S84OAS1, OAS2 and OAS3 restrict intracellular M. tb replication and enhance cytokine secretionGina Leisching0Victoria Cole1Aus T. Ali2Bienyameen Baker3NRF-DST Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Corresponding author.NRF-DST Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaDepartment of Pathology, National Health Laboratory Service, Tygerberg Hospital, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaNRF-DST Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South AfricaThe 2′,5′ (OASs) are known as mediators of the antiviral response system through activation of the RNA cleavage pathway. Interestingly, we observe OAS1, OAS2 and OAS3 upregulation in a number of gene expression signatures which discriminate active TB from latent TB infection, however their biological role during bacterial infection has not yet been elucidated. We observed that the expression of these genes was associated with pathogenicity and virulence of mycobacteria as infection with Mycobacterium bovis BCG failed to significantly induce OAS expression. Further, we observed that after silencing of these genes, M. tb CFU counts increased significantly 96 h post-infection in comparison to the respective controls. Luminex revealed that OAS silencing significantly decreased IL-1β, TNF-α and MCP-1 and had no effect of IL-10 secretion. We show for the first time that OAS1, 2 and 3 restrict intracellular pathogenic mycobacterial replication and enhance pro-inflammatory cytokine secretion. Keywords: M. tuberculosis, OAS, Host-defence, Anti-microbial, Pathogenesis, Virulencehttp://www.sciencedirect.com/science/article/pii/S1201971219300931
spellingShingle Gina Leisching
Victoria Cole
Aus T. Ali
Bienyameen Baker
OAS1, OAS2 and OAS3 restrict intracellular M. tb replication and enhance cytokine secretion
International Journal of Infectious Diseases
title OAS1, OAS2 and OAS3 restrict intracellular M. tb replication and enhance cytokine secretion
title_full OAS1, OAS2 and OAS3 restrict intracellular M. tb replication and enhance cytokine secretion
title_fullStr OAS1, OAS2 and OAS3 restrict intracellular M. tb replication and enhance cytokine secretion
title_full_unstemmed OAS1, OAS2 and OAS3 restrict intracellular M. tb replication and enhance cytokine secretion
title_short OAS1, OAS2 and OAS3 restrict intracellular M. tb replication and enhance cytokine secretion
title_sort oas1 oas2 and oas3 restrict intracellular m tb replication and enhance cytokine secretion
url http://www.sciencedirect.com/science/article/pii/S1201971219300931
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AT austali oas1oas2andoas3restrictintracellularmtbreplicationandenhancecytokinesecretion
AT bienyameenbaker oas1oas2andoas3restrictintracellularmtbreplicationandenhancecytokinesecretion