Fig. 1: BACH1 expression is elevated in patients displaying active disease and is associated with pulmonary necrosis in animal models of TB.
From: BACH1 promotes tissue necrosis and Mycobacterium tuberculosis susceptibility
a,d, Plasma samples collected from PTB (n = 30), TBI (n = 30) and HC (n = 30) patients from a Brazilian cohort. a, BACH1 mRNA expression in CD14+ monocytes (HC vs TBI, P < 0.0001; HC vs PTB, P < 0.0001; TBI vs PTB, P = 0.0216). b, BACH1 mRNA expression in total PBMC isolated from patients from a South African cohort34. c, log2 fold change (FC) of BACH1 mRNA expression in peripheral blood over time between bin-matched progressors (n = 44) and controls (n = 106) and modelled as nonlinear splines (black dashed line). Progressors are represented by light shading denoting 99% confidence interval (CI) and dark shading denoting 95% CI temporal trends. Dashed vertical line indicates the deviation time (day −238) calculated as the timepoint at which the 99% CI deviates from a log2 FC of 0. d, BACH1 mRNA expression in sorted neutrophils, monocytes and lymphocytes from PTB patients (n = 29) (neutrophils vs monocytes, P < 0.0001; neutrophils vs lymphocytes, P = 0.0216; monocytes vs lymphocytes, P = 0.011). e, BACH1 staining in a post-mortem PTB patient lung section. Yellow dashed lines delineate area surrounding necrotic zone within the granuloma. Data represent median values and interquartile ranges. Statistical significance was determined using a two-sided Kruskal–Wallis test with post-hoc Dunn’s test for multiple comparisons. Boxplots shown in b represent median (centre line), upper and lower quartiles (box limits) and the interquartile range (whiskers). Data shown in a–d are presented as mean ± s.e.m. and each symbol denotes an individual patient. NS, not significant. f, BACH1 staining in lung sections from 3 rhesus macaques. The top left panel shows a cellular granuloma (delineated by yellow dashed line); middle and bottom left panels show necrotic granulomas (delineated by yellow dashed line) with the necrotic core outlined by yellow dashed line and highlighted by an asterisk. g, Representative lung sections from Mtb-infected B6.Sst1S mice stained for Bach1. Dashed lines delineate the granuloma and asterisk indicates necrotic areas within the lesion. Red arrow points out cells resembling alveolar macrophages. Images shown are representative of those observed in 5 individual animals from 2 experiments.
