Detection of Mycobacterium tuberculosis DNA in CD34+ peripheral blood mononuclear cells of adults with tuberculosis infection and disease

Objectives To investigate whether Mycobacterium tuberculosis (Mtb) DNA is detected in peripheral blood mononuclear cells (PBMC) of subjects with tuberculosis (TB) or TB infection (TBI) living in a low TB burden country. Methods We prospectively enrolled 57 TB-patients, 41 TBI-subjects and 39 controls in Rome, Italy. PBMC were isolated, CD34+ and CD34− cells were immunomagnetic separated, DNA was extracted and digital PCR for IS6110 and rpoB sequences was used to detect Mtb DNA in PBMC subsets and unfractionated PBMC. Results We detected Mtb DNA at low copy number in CD34+ cells in 4/30 (13%) TB-patients, 2/24 (8%) TBI-subjects and 1/24 (4%) controls. Mtb DNA was detected in unfractionated PBMC in 3/51 (6%) TB-patients, 2/38 (5%) TBI-subjects and 2/36 (6%) controls. In CD34− cells only 1/31 (3%) TBI-subject was Mtb DNA positive. Conclusions Mtb DNA was detected at low frequency and levels in PBMC of TBI-subjects and TB-donors living in a low TB burden country. In particular, Mtb DNA was detected more frequently in CD34+ cells, supporting the hypothesis that these cells may represent a Mtb niche. This finding informs biological understanding of Mtb pathogenesis and may support development of a microbial blood biomarker for Mtb infection.