IFN-γ and IP-10 levels (pg/ml) in Antigen stimulated samples of patients with active and latent TB and a control group.

<p>Horizontal lines indicate median values. Controls are represented by ○, active TB by ▵, and LTBI by □. Open symbols represent IP-10, closed symbols represent IFNγ samples.</p

Concentration of IP-10 (pg/ml) in supernatants from: a) whole blood samples incubated with negative control antigen (background); b.) whole blood samples incubated with TB-specific antigens and negative control antigen, of children with active TB (n = 17), LTBI (n = 16) and a control group (n = 16).

<p>Horizontal lines indicate median values. Controls are represented by ○, active TB by ▵, and LTBI by □. Open symbols represent unstimulated, closed symbols represent antigen-stimulated samples.</p

Stimulation index of IP-10 and IFN-γ in active TB, LTBI and a control group.

<p>Horizontal lines indicate medians. Controls are represented by ○, active TB by ▵, and LTBI by □. Open symbols represent IP-10, closed symbols represent IFNγ samples.</p

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<p>Tuberculosis (TB) is still a global health concern, especially in resource-poor countries such as The Gambia. Defining protective immunity to TB is challenging: its pathogenesis is complex and involves several cellular components of the immune system. Recent works in vaccine development suggest important roles of the innate immunity in natural protection to TB, including natural killer (NK) cells. NK cells mediate cellular cytotoxicity and cytokine signaling in response to Mycobacterium tuberculosis (Mtb). NK cells can display specific memory-type markers to previous antigen exposure; thus, bridging innate and adaptive immunity. However, major knowledge gaps exist on the contribution of NK cells in protection against Mtb infection or TB. We performed a cross-sectional assessment of NK cells phenotype and function in four distinct groups of individuals: TB cases pre-treatment (n = 20) and post-treatment (n = 19), and household contacts with positive (n = 9) or negative (n = 18) tuberculin skin test (TST). While NK cells frequencies were similar between all groups, significant decreases in interferon-γ expression and degranulation were observed in NK cells from TB cases pre-treatment compared to post-treatment. Conversely, CD57 expression, a marker of advanced NK cells differentiation, was significantly lower in cases post-treatment compared to pre-treatment. Finally, NKG2C, an activation and imprinted-NK memory marker, was significantly increased in TST+ (latently infected) compared to TB cases pre-treatment and TST− (uninfected) individuals. The results of this study provide valuable insights into the role of NK cells in Mtb infection and TB disease, demonstrating potential markers for distinguishing between infection states and monitoring of TB treatment response.</p

Additional file 1: Table S1. of Monocyte unresponsiveness and impaired IL1β, TNFι and IL7 production are associated with a poor outcome in Malawian adults with pulmonary tuberculosis

Median and IQR for responses to stimulation with heat killed Mycobacterium Tuberculosis (H37Rv) or Lipopolysaccaride (LPS). P-values are derived from Mann-Whitney U tests. 11 analyses were performed for each stimulus, giving a corrected p value of 0.0045 using the Bonferroni correction. (DOCX 17 kb

Additional file 2: Figure S1. of Monocyte unresponsiveness and impaired IL1β, TNFι and IL7 production are associated with a poor outcome in Malawian adults with pulmonary tuberculosis

Gating strategy to identify monocyte populations. The first plot represents the forward scatter- side scatter characteristics and the second the separation according to CD14 and CD16 staining. (JPEG 61 kb

Summary of participants' responses regarding their access to the Xpert MTB/RIF assay according to country.

<p>Summary of participants' responses regarding their access to the Xpert MTB/RIF assay according to country.</p

Summary of participants' responses regarding their access to the Xpert MTB/RIF assay according to country.

<p>Summary of participants' responses regarding their access to the Xpert MTB/RIF assay according to country.</p

Summary of participants' responses regarding their access to immunological, conventional microbiological and molecular tests for tuberculosis.

<p>Summary of participants' responses regarding their access to immunological, conventional microbiological and molecular tests for tuberculosis.</p

Heatmap of cytokine profiles in patients with low and high bacterial loads.

<p>Cytokine levels (pg/ml) for unstimulated (NIL) and sputum supernatants were analysed using a 27-plex cytokine array. Subjects were grouped into those with low bacterial load (below the median of 48059 copies/ml) and high bacterial load (above median). Data were analysed using a Mann-Whitney U-test. NS = not significant. Colour indicates low (blue) to high (red) cytokine levels.</p