Aggregated Mycobacterium tuberculosis Enhances the Inflammatory Response
Name
fmicb-12-757134.pdf
Description
Published version
Size
2.58 MB
Format
Adobe PDF
Checksum (MD5)
36098382de473847812a8cf70002ed9a
Author(s)
Rodel, Hylton E
Ferreira, Isabella ATM
Ziegler, Carly GK
Ganga, Yashica
Bernstein, Mallory
Hwa, Shi-Hsia
Nargan, Kievershen
Lustig, Gila
Kaplan, Gilla
Noursadeghi, Mahdad
Date Issued
2021
Journal
Frontiers in Microbiology
Publisher
Frontiers Media SA
Citation
Rodel, Hylton E, Ferreira, Isabella ATM, Ziegler, Carly GK, Ganga, Yashica, Bernstein, Mallory et al. 2021. "Aggregated Mycobacterium tuberculosis Enhances the Inflammatory Response." Frontiers in Microbiology, 12.
Version
Final published version
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.
MIT Department
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.3389/fmicb.2021.757134
