Aggregated Mycobacterium tuberculosis Enhances the Inflammatory Response

Mycobacterium tuberculosis (Mtb) bacilli readily aggregate. We previously reported that Mtb aggregates lead to phagocyte death and subsequent efficient replication in the dead infected cells. Here, we examined the transcriptional response of human monocyte derived macrophages to phagocytosis of aggr...

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Autores principales:	Hylton E. Rodel, Isabella A. T. M. Ferreira, Carly G. K. Ziegler, Yashica Ganga, Mallory Bernstein, Shi-Hsia Hwa, Kievershen Nargan, Gila Lustig, Gilla Kaplan, Mahdad Noursadeghi, Alex K. Shalek, Adrie J. C. Steyn, Alex Sigal
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Mycobacterium tuberculosis TB pathogenesis aggregation inflammation TNF-alpha phagocytosis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2c87105ebf6a454b849cec67673a9715
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spelling	oai:doaj.org-article:2c87105ebf6a454b849cec67673a97152021-12-02T10:03:45ZAggregated Mycobacterium tuberculosis Enhances the Inflammatory Response1664-302X10.3389/fmicb.2021.757134https://doaj.org/article/2c87105ebf6a454b849cec67673a97152021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.757134/fullhttps://doaj.org/toc/1664-302XMycobacterium tuberculosis (Mtb) bacilli readily aggregate. We previously reported that Mtb aggregates lead to phagocyte death and subsequent efficient replication in the dead infected cells. Here, we examined the transcriptional response of human monocyte derived macrophages to phagocytosis of aggregated Mtb relative to phagocytosis of non-aggregated single or multiple bacilli. Infection with aggregated Mtb led to an early upregulation of pro-inflammatory associated genes and enhanced TNFα signaling via the NFκB pathway. These pathways were significantly more upregulated relative to infection with single or multiple non-aggregated bacilli per cell. Phagocytosis of aggregates led to a decreased phagosome acidification on a per bacillus basis and increased phagocyte cell death, which was not observed when Mtb aggregates were heat killed prior to phagocytosis. Mtb aggregates, observed in a granuloma from a patient, were found surrounding a lesion cavity. These observations suggest that TB aggregation may be a mechanism for pathogenesis. They raise the possibility that aggregated Mtb, if spread from individual to individual, could facilitate increased inflammation, Mtb growth, and macrophage cell death, potentially leading to active disease, cell necrosis, and additional cycles of transmission.Hylton E. RodelHylton E. RodelIsabella A. T. M. FerreiraCarly G. K. ZieglerCarly G. K. ZieglerCarly G. K. ZieglerCarly G. K. ZieglerYashica GangaMallory BernsteinShi-Hsia HwaShi-Hsia HwaKievershen NarganGila LustigGilla KaplanMahdad NoursadeghiAlex K. ShalekAlex K. ShalekAlex K. ShalekAlex K. ShalekAdrie J. C. SteynAdrie J. C. SteynAdrie J. C. SteynAlex SigalAlex SigalAlex SigalAlex SigalFrontiers Media S.A.articleMycobacterium tuberculosisTB pathogenesisaggregationinflammationTNF-alphaphagocytosisMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mycobacterium tuberculosis TB pathogenesis aggregation inflammation TNF-alpha phagocytosis Microbiology QR1-502
spellingShingle	Mycobacterium tuberculosis TB pathogenesis aggregation inflammation TNF-alpha phagocytosis Microbiology QR1-502 Hylton E. Rodel Hylton E. Rodel Isabella A. T. M. Ferreira Carly G. K. Ziegler Carly G. K. Ziegler Carly G. K. Ziegler Carly G. K. Ziegler Yashica Ganga Mallory Bernstein Shi-Hsia Hwa Shi-Hsia Hwa Kievershen Nargan Gila Lustig Gilla Kaplan Mahdad Noursadeghi Alex K. Shalek Alex K. Shalek Alex K. Shalek Alex K. Shalek Adrie J. C. Steyn Adrie J. C. Steyn Adrie J. C. Steyn Alex Sigal Alex Sigal Alex Sigal Alex Sigal Aggregated Mycobacterium tuberculosis Enhances the Inflammatory Response
description	Mycobacterium tuberculosis (Mtb) bacilli readily aggregate. We previously reported that Mtb aggregates lead to phagocyte death and subsequent efficient replication in the dead infected cells. Here, we examined the transcriptional response of human monocyte derived macrophages to phagocytosis of aggregated Mtb relative to phagocytosis of non-aggregated single or multiple bacilli. Infection with aggregated Mtb led to an early upregulation of pro-inflammatory associated genes and enhanced TNFα signaling via the NFκB pathway. These pathways were significantly more upregulated relative to infection with single or multiple non-aggregated bacilli per cell. Phagocytosis of aggregates led to a decreased phagosome acidification on a per bacillus basis and increased phagocyte cell death, which was not observed when Mtb aggregates were heat killed prior to phagocytosis. Mtb aggregates, observed in a granuloma from a patient, were found surrounding a lesion cavity. These observations suggest that TB aggregation may be a mechanism for pathogenesis. They raise the possibility that aggregated Mtb, if spread from individual to individual, could facilitate increased inflammation, Mtb growth, and macrophage cell death, potentially leading to active disease, cell necrosis, and additional cycles of transmission.
format	article
author	Hylton E. Rodel Hylton E. Rodel Isabella A. T. M. Ferreira Carly G. K. Ziegler Carly G. K. Ziegler Carly G. K. Ziegler Carly G. K. Ziegler Yashica Ganga Mallory Bernstein Shi-Hsia Hwa Shi-Hsia Hwa Kievershen Nargan Gila Lustig Gilla Kaplan Mahdad Noursadeghi Alex K. Shalek Alex K. Shalek Alex K. Shalek Alex K. Shalek Adrie J. C. Steyn Adrie J. C. Steyn Adrie J. C. Steyn Alex Sigal Alex Sigal Alex Sigal Alex Sigal
author_facet	Hylton E. Rodel Hylton E. Rodel Isabella A. T. M. Ferreira Carly G. K. Ziegler Carly G. K. Ziegler Carly G. K. Ziegler Carly G. K. Ziegler Yashica Ganga Mallory Bernstein Shi-Hsia Hwa Shi-Hsia Hwa Kievershen Nargan Gila Lustig Gilla Kaplan Mahdad Noursadeghi Alex K. Shalek Alex K. Shalek Alex K. Shalek Alex K. Shalek Adrie J. C. Steyn Adrie J. C. Steyn Adrie J. C. Steyn Alex Sigal Alex Sigal Alex Sigal Alex Sigal
author_sort	Hylton E. Rodel
title	Aggregated Mycobacterium tuberculosis Enhances the Inflammatory Response
title_short	Aggregated Mycobacterium tuberculosis Enhances the Inflammatory Response
title_full	Aggregated Mycobacterium tuberculosis Enhances the Inflammatory Response
title_fullStr	Aggregated Mycobacterium tuberculosis Enhances the Inflammatory Response
title_full_unstemmed	Aggregated Mycobacterium tuberculosis Enhances the Inflammatory Response
title_sort	aggregated mycobacterium tuberculosis enhances the inflammatory response
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/2c87105ebf6a454b849cec67673a9715
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Aggregated Mycobacterium tuberculosis Enhances the Inflammatory Response

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