Cox proportional hazard regression for development of tuberculosis

<p>Cox proportional hazard regression for development of tuberculosis</p

Flow chart of enrollment of participants.

<p>Flow chart of enrollment of participants.</p

Regular Sputum Check-Up for Early Diagnosis of Tuberculosis after Exposure in Healthcare Facilities - Fig 3

<p>Kaplan-Meier analysis based on body mass index (A) and contact duration (B).</p

Using sputum check to early detect new tuberculosis cases based on CXR alone or combinational CCB score.

<p>Receiver operator characteristic curve (A). Separate percentage (B) and diagnostic accuracy (C) by CCB score. CCB score: CXR, Contact-duration and BMI score.</p

Characteristics of the 16 newly diagnosed TB cases

<p>Characteristics of the 16 newly diagnosed TB cases</p

Epidemic curve of the reported TB outbreak.

<p>Epidemic curve of the reported TB outbreak.</p

Mycobacterial infection induces higher interleukin-1β and dysregulated lung inflammation in mice with defective leukocyte NADPH oxidase

<div><p>Granulomatous inflammation causes severe tissue damage in mycobacterial infection while redox status was reported to be crucial in the granulomatous inflammation. Here, we used a NADPH oxidase 2 (NOX2)-deficient mice (<i>Ncf1</i>^<i>-/-</i>) to investigate the role of leukocyte-produced reactive oxygen species (ROS) in mycobacterium-induced granulomatous inflammation. We found poorly controlled mycobacterial proliferation, significant body weight loss, and a high mortality rate after <i>M</i>. <i>marinum</i> infection in <i>Ncf1</i>^<i>-/-</i> mice. Moreover, we noticed loose and neutrophilic granulomas and higher levels of interleukin (IL)-1β and neutrophil chemokines in <i>Ncf1</i>^<i>-/-</i> mice when compared with those in wild type mice. The lack of ROS led to reduced production of IL-1β in macrophages, whereas neutrophil elastase (NE), an abundant product of neutrophils, may potentially exert increased inflammasome-independent protease activity and lead to higher IL-1β production. Moreover, we showed that the abundant NE and IL-1β were present in the caseous granulomatous inflammation of human TB infection. Importantly, blocking of IL-1β with either a specific antibody or a recombinant IL-1 receptor ameliorated the pulmonary inflammation. These findings revealed a novel role of ROS in the early pathogenesis of neutrophilic granulomatous inflammation and suggested a potential role of IL-1 blocking in the treatment of mycobacterial infection in the lung.</p></div

Additional file 1: of Using genotyping to delineate tuberculosis transmission in long-term care facilities: single facility 4-year experience

Dataset of demographic and laboratory data. (XLSX 16 kb

Increased severity and mortality of <i>M</i>. <i>marinum</i> pulmonary infection in <i>Ncf1</i>^<i>-/-</i> mice.

<p><i>Ncf1</i>^-/- (loss of function mutation in p47phox) and WT controls were intra-tracheal injected with <i>M</i>. <i>marinum</i> (3 x 10⁷ CFU). Survival (A) and changes in body weight (B) were monitored over the 28 days period following <i>M</i>. <i>marinum</i> infection in WT (n = 20) and <i>Ncf1</i>^-/- mice (n = 23). The number of viable mycobacteria (C) was determined at 7 days and 14 days after <i>M</i>. <i>marinum</i> infection. Data are shown as a mean log of CFU per paired-lung (5 mice per group). The high correlation between changes in body weight and a number of viable mycobacteria in lungs was demonstrated in (D). Data represented mean ± sd. The experiments were analyzed with Log-rank test (A), Kruskal-Wallis test (C), and Spearman’s rank correlation analysis (D) *p < 0.05; **p < 0.005. These experiments were repeated twice with similar results.</p

High levels of IL-1β and neutrophilic chemokines in <i>M</i>. <i>marinum</i>-infected <i>Ncf1</i>^-/- mice.

<p>Cytokine and chemokine responses to <i>M</i>. <i>marinum</i> infection (3 x 10⁶ CFU). Cytokines of innate immunity including IL-1β (A), TNF-α (B) and IL-6 (C); cytokines of adaptive immunity including IFN-γ (D), IL-10 (E) and IL-17 A(F), and neutrophilc chemokines including CXCL5 (G), CCL5 (H) and CXCL1 (I) were assessed in lung homogenates obtained 7 days and 14 days after <i>M</i>. <i>marinum</i> infection (<i>3</i> x 10⁶ CFU). Data represent mean ± sd (n = 4–7 mice each group) The experiments were analyzed with Kruskal-Wallis test. *p < 0.05; **p < 0.005 and repeated with similar results.</p