Rodel, HE;
Ferreira, IATM;
Ziegler, CGK;
Ganga, Y;
Bernstein, M;
Hwa, S-H;
Nargan, K;
... Sigal, A; + view all
(2021)
Aggregated Mycobacterium tuberculosis Enhances the Inflammatory Response.
Frontiers in Microbiology
, 12
, Article 757134. 10.3389/fmicb.2021.757134.
Preview |
Text
fmicb-12-757134.pdf - Published Version Download (2MB) | Preview |
Abstract
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.
| Type: | Article |
|---|---|
| Title: | Aggregated Mycobacterium tuberculosis Enhances the Inflammatory Response |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fmicb.2021.757134 |
| Publisher version: | https://doi.org/10.3389/fmicb.2021.757134 |
| Language: | English |
| Additional information: | Copyright © 2021 Rodel, Ferreira, Ziegler, Ganga, Bernstein, Hwa, Nargan, Lustig, Kaplan, Noursadeghi, Shalek, Steyn and Sigal. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | Mycobacterium tuberculosis, TB pathogenesis, aggregation, inflammation, TNF-alpha, phagocytosis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10141208 |
Archive Staff Only
 |
View Item |
