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<p><i>Mycobacterium avium&#xa0;</i>subsp.&#xa0;<i>hominissuis</i>&#xa0;(<i>M. avium</i>) 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 <i>M. avium.</i> We hypothesized that <i>M. avium</i> eDNA might play a role in macrophages survival. To investigate the macrophage response to <i>M. avium</i> eDNA, we utilized two virulent strains of <i>M. avium</i>, eDNA-deficient mutants, and nonvirulent <i>Mycobacterium smegmatis</i>. eDNA-deficient mutants were attenuated at macrophage survival and yielded significantly higher IL-1β than wildtype bacterium, while <i>M. avium,</i> but not <i>M. smegmatis</i>, suppresses IL-1β production and NLRP3 expression by host macrophages. We also observed that <i>M. avium</i> triggered IFN-β production in a DNA-dependent manner but did not have an effect on cGAS expression. These data indicate that <i>M. avium</i> strains modulate macrophage responses in an eDNA dependent manner.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月25日

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  • Jayanthi J. Joseph,
  • Amy Leestemaker-Palmer,
  • Luiz E. Bermudez

摘要

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.