Blood DNA methylation altered by Mycobacterium tuberculosis infection in mice

Knowing when a person was infected with Mycobacterium tuberculosis (M.tb) is critical as recent infection is the strongest clinical risk factor for progression to TB disease in immunocompetent individuals. However, time since M.tb infection is very difficult to determine in routine clinical practice. We determined whether DNA methylation patterns in the blood correlate with time since M.tb infection or exposure to develop a biomarker for recent exposure. As proof of concept, we found a DNA methylation signature that is present during early infection of mice that persists for at least 5 months post-infection. Blood was collected from 54 C57BL/6 mice and 46 BALB/c mice infected with a low dose of M.tb (Erdman), as well as 23 C57BL/6 mice and 28 BALB/c mice that served as uninfected, age-matched controls. Blood was collected at days 7, 14, 30, 62, 90, 120 and 153 post-infection. Whole blood was subjected to reduced representation bisulfite sequencing. We identify stable DNA methylation changes associated with infection.