Fig. 1: M. tuberculosis clinical isolates associated with severe TB induce lower cytokine responses.

a The clinical data for 681 adult pulmonary TB (pTB) cases were reviewed and classified according to the absence or presence of comorbidities. b Top panel: genetic makeup through a validated panel of autosomal ancestry-informative markers of reference populations of African, European, East Asian, and Native American biogeographical origin. Bottom panel: the genetic ancestry for a group of 60 TB patients was determined, together with TB contacts from the same area and a reference Portuguese population. Represented are European ancestry in blue, African in orange, East Asian in pink and Native American in purple. c Clinical decision system developed to classify the severity of TB at presentation in mild, moderate or severe. d Patients who had no known comorbidities (n = 133) were classified into mild, moderate, or severe TB cases at presentation. e M. tuberculosis isolates recovered for 117 of the 133 selected TB patients were classified into lineages and those belonging to lineage 4 (L4) were further classified into L4.3/LAM, L4.1.1/X, L4.1.2/Haarlem or other lineage 4 sublineages. f Mild, moderate, and severe TB cases, as determined in d, were stratified according to the sublineage, the infecting bacteria belonged to. Statistical analysis was performed with Fisher’s exact test. g PBMC from 8-10 IGRA + donors were infected with L4 M. tuberculosis isolated from mild (n = 10), moderate (n = 9), or severe (n = 7) TB patients. An MOI of 1 was used and 24 h post-infection the amounts of secreted IL-1β, IL-12p40, IL-10, and IFN-β quantified. Represented are bean plots for each cytokine. Black lines show the medians; white lines represent individual data points; polygons represent the estimated density of the data. IFN-β was undetected for all conditions. Statistical analysis was performed with Pearson correlation; R and p-values were: IL-1β R = –0.3471; R2 = 0.1205; p < 0.00001; IL-12 R = –0.3419; R2 = 0.1169; p < 0.00001; and IL-10 R = –0.1918; R2 = 0.0368; p = 0.002473. CRP C-reactive protein, Hb hemoglobin, LAM Latin-American and Mediterranean, N no, TB tuberculosis, Y yes.