CD14⁺⁺CD16^- classical monocyte subset secreting IL-1ß and IL-10 is associated with 'Tuberculosis Resisters' phenotype

Mycobacterium tuberculosis (M.tb) infection can lead to various outcomes, including active tuberculosis or latent tuberculosis infection (LTBI). Household contacts of TB cases have a high risk of acquiring LTBI. However, some contacts exposed to M.tb remain negative for tuberculin skin test (TST) and interferon-gamma release assay (IGRA) tests and are called 'TB resisters'. Characterization of immune responses in 'TB resisters' may help to understand correlates of protection against M.tb. Based on the TST and IGRA tests, household contacts were divided into 'LTBI' and 'TB Resisters'. Peripheral blood mononuclear cells (PBMCs) of the study participants were isolated and processed to characterize the monocyte subsets based on CD14 and CD16 expression in flow cytometry. Monocyte intracellular cytokine expression (IL-10, IL-6, TNF-α and IL-1ß) was assessed after Lipopolysaccharide (LPS) stimulation. LTBI and active TB patients showed a higher frequency of intermediate and non-classical monocyte subsets depicting the infectious stage. Higher frequency of classical monocyte subsets was associated with 'TB resisters'. Marked expression of IL-1ß and a higher monocyte to lymphocytes (M/L) ratio was seen in PTB, LTBI and TB resister groups compared to healthy controls indicating active disease or exposure to M.tb. Classical Monocytes (CM) were further found to be associated with higher expression of IL-1ß and IL-10 in the 'TB resister group', which might help in the clearance of infection at an early stage. LTBI and PTB showed significantly higher TNF-α producing monocytes than healthy controls and 'TB Resisters'. IL6-producing monocytes were significantly higher in LTBI compared to other study groups. These findings could further be explored with follow-up in cohort of 'TB resisters'. Also, the role of IL-1ß and IL10 secreting classical monocytes in early clearance of infection could be explored with in vitro mechanistic studies.