Export of eDNA is a mechanism used by Mycobacterium avium subsp. hominissuis for survival within host macrophages.

Mycobacterium avium subsp. hominissuis (M. avium) is a pathogen that causes pulmonary and systemic infection in humans. Mycobacterial infection activates both pro-inflammatory and anti-inflammatory pathways modulating these routes to escape killing. eDNA has a role for environmental survival and biofilm formation of M. avium. We hypothesized that M. avium eDNA might play a role in macrophages survival. To investigate the macrophage response to M. avium eDNA, we utilized two virulent strains of M. avium, eDNA-deficient mutants, and nonvirulent Mycobacterium smegmatis. eDNA-deficient mutants were attenuated at macrophage survival and yielded significantly higher IL-1β than wildtype bacterium, while M. avium, but not M. smegmatis, suppresses IL-1β production and NLRP3 expression by host macrophages. We also observed that M. avium triggered IFN-β production in a DNA-dependent manner but did not have an effect on cGAS expression. These data indicate that M. avium strains modulate macrophage responses in an eDNA dependent manner.