Distinct host-immune response toward species related intracellular mycobacterial killing: A transcriptomic study

The comparison of the host immune response when challenged with pathogenic and nonpathogenic species of mycobacteria can provide answers to the unresolved question of how pathogens subvert or inhibit an effective response. We infected human monocyte derived macrophages (hMDMs) with different species...

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Autores principales:	Abhilasha Madhvi, Hridesh Mishra, Novel N. Chegou, Gerard Tromp, Carel J. Van Heerden, R. D. Pietersen, Gina Leisching, Bienyameen Baker
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2020
Materias:	mycobacteria pathogenic nonpathogenic host immune response amplicon-based rna sequencing detergent-free media Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/655a5e9797a442a49fce39cc6dbda58a
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spelling	oai:doaj.org-article:655a5e9797a442a49fce39cc6dbda58a2021-11-17T14:21:57ZDistinct host-immune response toward species related intracellular mycobacterial killing: A transcriptomic study2150-55942150-560810.1080/21505594.2020.1726561https://doaj.org/article/655a5e9797a442a49fce39cc6dbda58a2020-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2020.1726561https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608The comparison of the host immune response when challenged with pathogenic and nonpathogenic species of mycobacteria can provide answers to the unresolved question of how pathogens subvert or inhibit an effective response. We infected human monocyte derived macrophages (hMDMs) with different species of mycobacteria, in increasing order of pathogenicity, i.e. M. smegmatis, M. bovis BCG, and M. tuberculosis R179 that had been cultured in the absence of detergents. RNA was isolated post-infection and transcriptomic analysis using amplicons (Ampliseq) revealed 274 differentially expressed genes (DEGs) across three species, out of which we selected 19 DEGs for further validation. We used qRT-PCR to confirm the differential expression of 19 DEGs. We studied biological network through Ingenuity Pathway Analysis® (IPA) which revealed up-regulated pathways of the interferon and interleukin family related to the killing of M. smegmatis. Apart from interferon and interleukin family, we found one up-regulated (EIF2AK2) and two down-regulated (MT1A and TRIB3) genes as unique potential targets found by Ampliseq and qRT-PCR which may be involved in the intracellular mycobacterial killing. The roles of these genes have not previously been described in tuberculosis. Multiplex ELISA of culture supernatants showed increased host immune response toward M. smegmatis as compared to M. bovis BCG and M.tb R179. These results enhance our understanding of host immune response against M.tb infection.Abhilasha MadhviHridesh MishraNovel N. ChegouGerard TrompCarel J. Van HeerdenR. D. PietersenGina LeischingBienyameen BakerTaylor & Francis Grouparticlemycobacteriapathogenicnonpathogenichost immune responseamplicon-based rna sequencingdetergent-free mediaInfectious and parasitic diseasesRC109-216ENVirulence, Vol 11, Iss 1, Pp 170-182 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	mycobacteria pathogenic nonpathogenic host immune response amplicon-based rna sequencing detergent-free media Infectious and parasitic diseases RC109-216
spellingShingle	mycobacteria pathogenic nonpathogenic host immune response amplicon-based rna sequencing detergent-free media Infectious and parasitic diseases RC109-216 Abhilasha Madhvi Hridesh Mishra Novel N. Chegou Gerard Tromp Carel J. Van Heerden R. D. Pietersen Gina Leisching Bienyameen Baker Distinct host-immune response toward species related intracellular mycobacterial killing: A transcriptomic study
description	The comparison of the host immune response when challenged with pathogenic and nonpathogenic species of mycobacteria can provide answers to the unresolved question of how pathogens subvert or inhibit an effective response. We infected human monocyte derived macrophages (hMDMs) with different species of mycobacteria, in increasing order of pathogenicity, i.e. M. smegmatis, M. bovis BCG, and M. tuberculosis R179 that had been cultured in the absence of detergents. RNA was isolated post-infection and transcriptomic analysis using amplicons (Ampliseq) revealed 274 differentially expressed genes (DEGs) across three species, out of which we selected 19 DEGs for further validation. We used qRT-PCR to confirm the differential expression of 19 DEGs. We studied biological network through Ingenuity Pathway Analysis® (IPA) which revealed up-regulated pathways of the interferon and interleukin family related to the killing of M. smegmatis. Apart from interferon and interleukin family, we found one up-regulated (EIF2AK2) and two down-regulated (MT1A and TRIB3) genes as unique potential targets found by Ampliseq and qRT-PCR which may be involved in the intracellular mycobacterial killing. The roles of these genes have not previously been described in tuberculosis. Multiplex ELISA of culture supernatants showed increased host immune response toward M. smegmatis as compared to M. bovis BCG and M.tb R179. These results enhance our understanding of host immune response against M.tb infection.
format	article
author	Abhilasha Madhvi Hridesh Mishra Novel N. Chegou Gerard Tromp Carel J. Van Heerden R. D. Pietersen Gina Leisching Bienyameen Baker
author_facet	Abhilasha Madhvi Hridesh Mishra Novel N. Chegou Gerard Tromp Carel J. Van Heerden R. D. Pietersen Gina Leisching Bienyameen Baker
author_sort	Abhilasha Madhvi
title	Distinct host-immune response toward species related intracellular mycobacterial killing: A transcriptomic study
title_short	Distinct host-immune response toward species related intracellular mycobacterial killing: A transcriptomic study
title_full	Distinct host-immune response toward species related intracellular mycobacterial killing: A transcriptomic study
title_fullStr	Distinct host-immune response toward species related intracellular mycobacterial killing: A transcriptomic study
title_full_unstemmed	Distinct host-immune response toward species related intracellular mycobacterial killing: A transcriptomic study
title_sort	distinct host-immune response toward species related intracellular mycobacterial killing: a transcriptomic study
publisher	Taylor & Francis Group
publishDate	2020
url	https://doaj.org/article/655a5e9797a442a49fce39cc6dbda58a
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Distinct host-immune response toward species related intracellular mycobacterial killing: A transcriptomic study

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