Abstract:
:Dissecting the in vivo host-pathogen interplay is crucial to understanding the molecular mechanisms governing control or progression of intracellular infections. In this work, we explore the in vivo molecular dynamics of Mtb infection by performing dual RNA-seq on Mycobacterium tuberculosis-infected, ontogenetically distinct macrophage lineages isolated directly from murine lungs. We first define an in vivo signature of 180 genes specifically upregulated by Mtb in mouse lung macrophages, then we uncover a divergent transcriptional response of the bacteria between alveolar macrophages that appear to sustain Mtb growth through increased access to iron and fatty acids and interstitial macrophages that restrict Mtb growth through iron sequestration and higher levels of nitric oxide. We use an enrichment protocol for bacterial transcripts, which enables us to probe Mtb physiology at the host cell level in an in vivo environment, with broader application in understanding the infection dynamics of intracellular pathogens in general.
journal_name
Cell Repjournal_title
Cell reportsauthors
Pisu D,Huang L,Grenier JK,Russell DGdoi
10.1016/j.celrep.2019.12.033subject
Has Abstractpub_date
2020-01-14 00:00:00pages
335-350.e4issue
2issn
2211-1247pii
S2211-1247(19)31683-3journal_volume
30pub_type
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