Eating the Enemy: Mycoplasma Strategies to Evade Neutrophil Extracellular Traps (NETs) Promoting Bacterial Nucleotides Uptake and Inflammatory Damage

Neutrophils are effector cells involved in the innate immune response against infection; they kill infectious agents in the intracellular compartment (phagocytosis) or in the extracellular milieu (degranulation). Moreover, neutrophils release neutrophil extracellular traps (NETs), complex structures composed of a scaffold of decondensed DNA associated with histones and antimicrobial compounds; NETs entrap infectious agents, preventing their spread and promoting their clearance. NET formation is triggered by microbial compounds, but many microorganisms have evolved several strategies for NET evasion. In addition, the dysregulated production of NETs is associated with chronic inflammatory diseases. Mycoplasmas are reduced genome bacteria, able to induce chronic infections with recurrent inflammatory symptoms. Mycoplasmas' parasitic lifestyle relies on metabolite uptake from the host. Mycoplasmas induce NET release, but their surface or secreted nucleases digest the NETs' DNA scaffold, allowing them to escape from entrapment and providing essential nucleotide precursors, thus promoting the infection. The presence of Mycoplasma species has been associated with chronic inflammatory disorders, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, and cancer. The persistence of mycoplasma infection and prolonged NET release may contribute to the onset of chronic inflammatory diseases and needs further investigation and insights.