Neutrophil Extracellular Traps as Novel Treatment Targets in Infectious and inflammatory Disease Clinical Applications of Immunothrombosis and 'Omics in Sepsis (Planned by VCCIS)

Presentation Description / Summary: Both infectious and inflammatory stimuli induce the release of neutrophil extracellular traps (NETs), webs of negatively charged cell-free (cf) DNA complexed with positively charged histones and antimicrobial proteins such as myeloperoxidase (MPO), that capture and kill pathogens. Despite their protective role in the initial stages of sepsis, excessive NET release, also termed NETosis, accompanied by NET degradation, can injure the microvasculature and induce organ dysfunction. Recently, elevated NET degradation products (NDPs), including cfDNA, histones, and MPO, have been associated with increased disease severity in sepsis and COVID-19, further raising interest in targeting NETs in inflammatory disease. The most common proposed strategies are to eliminate NETs, either by preventing their release, or by degrading them with nucleases. However, NET-inhibition may impede the innate immune response and can be difficult to achieve in acute-onset conditions such as sepsis. On the other hand, approaches that accelerate NET degradation have met with mixed results in murine studies, raising the concern that this strategy may lead to liberation of NET-captured pathogens while increasing circulating levels of harmful NDPs. Alternative NET-directed strategies include therapies that neutralize, sequester, or remove NDPs from the circulation.

Learner Outcomes: To come