In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 12 ( 2022-12-1), p. e0278295-
Kurzfassung:
Mycobacterium tuberculosis ( M . tb ) causes tuberculosis (TB) and remains one of the leading causes of mortality due to an infectious pathogen. Host immune responses have been implicated in driving the progression from infection to severe lung disease. We analyzed longitudinal RNA sequencing (RNAseq) data from the whole blood of 74 TB progressors whose samples were grouped into four six-month intervals preceding diagnosis (the GC6-74 study). We additionally analyzed RNAseq data from an independent cohort of 90 TB patients with positron emission tomography-computed tomography (PET-CT) scan results which were used to categorize them into groups with high and low levels of lung damage (the Catalysis TB Biomarker study). These groups were compared to non-TB controls to obtain a complete whole blood transcriptional profile for individuals spanning from early stages of M . tb infection to TB diagnosis. The results revealed a steady increase in the number of genes that were differentially expressed in progressors at time points closer to diagnosis with 278 genes at 13–18 months, 742 at 7–12 months and 5,131 detected 1–6 months before diagnosis and 9,205 detected in TB patients. A total of 2,144 differentially expressed genes were detected when comparing TB patients with high and low levels of lung damage. There was a large overlap in the genes upregulated in progressors 1–6 months before diagnosis (86%) with those in TB patients. A comprehensive pathway analysis revealed a potent activation of neutrophil and platelet mediated defenses including neutrophil and platelet degranulation, and NET formation at both time points. These pathways were also enriched in TB patients with high levels of lung damage compared to those with low. These findings suggest that neutrophils and platelets play a critical role in TB pathogenesis, and provide details of the timing of specific effector mechanisms that may contribute to TB lung pathology.
Materialart:
Online-Ressource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0278295
DOI:
10.1371/journal.pone.0278295.g001
DOI:
10.1371/journal.pone.0278295.g002
DOI:
10.1371/journal.pone.0278295.g003
DOI:
10.1371/journal.pone.0278295.g004
DOI:
10.1371/journal.pone.0278295.g005
DOI:
10.1371/journal.pone.0278295.g006
DOI:
10.1371/journal.pone.0278295.t001
DOI:
10.1371/journal.pone.0278295.t002
DOI:
10.1371/journal.pone.0278295.t003
DOI:
10.1371/journal.pone.0278295.s001
DOI:
10.1371/journal.pone.0278295.s002
DOI:
10.1371/journal.pone.0278295.s003
DOI:
10.1371/journal.pone.0278295.s004
DOI:
10.1371/journal.pone.0278295.s005
DOI:
10.1371/journal.pone.0278295.s006
DOI:
10.1371/journal.pone.0278295.s007
DOI:
10.1371/journal.pone.0278295.s008
DOI:
10.1371/journal.pone.0278295.r001
DOI:
10.1371/journal.pone.0278295.r002
DOI:
10.1371/journal.pone.0278295.r003
DOI:
10.1371/journal.pone.0278295.r004
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2022
ZDB Id:
2267670-3
