The role of autophagy associated gene expressions in the progression from latent TB infection to active pulmonary TB disease

Abstract

<b>Background:</b> Autophagy serves as the first line defensive mechanism for the clearance of mycobacterium tuberculosis (TB) in the human innate and adaptive immune cells, but its clinical implication in active TB disease or latent TB infection (LTBI) is poorly understood. <b>Aim:</b> The study investigates if autophagy flux of immune cells varies among groups with active TB, LTBI, and non-infected healthy subjects (NIHS). Method: Autophagy-associated gene (ATG) protein expressions of blood immune cells were measured in 44 patients with sputum culture (+) active pulmonary TB disease, 23 subjects with LTBI (IGRA+), and 12 NIHS(IGRA-) by flowcytometry method. <b>Results:</b> LC3B expression of either CD14+CD209- M1 or CD14+CD209+ M2a monocyte was increased in active TB group as compared with either LTBI or NIHS group, while ATG5 expression of M2a was increased in active TB group versus NIHS group. Subgroup analysis showed that LC3B, ATG5, and P62 expressions of CD3+CD8+ cytotoxic T cells were all increased in active TB patients with high bacterial burden. ATG5 or P62 expression of CD16+ neutrophil, and LC3B expression of either CD3+CD4+ helper T cell or cytotoxic T cell were reduced. LC3b, ATG5, and p62 expressions of human monocytic THP-1 cells were increased in response to ESAT-6 stimuli in vitro, but decreased to Ag85A and H37Rv whole M.tb cell stimuli. <b>Conclusions:</b> Increased LC3B and ATG5 expressions of blood monocyte may serve as a marker of progression from latent TB infection to active TB disease. Combining M2a-LC3B% and BMI, a prediction score could be calculated to display optimal discrimination for active TB disease from LTBI.