What are the mechanisms for NETs formation?
—What are the relationships among NETs formation and autophagy, mitochondrial DNA release, and histone citrullation?
—Are all NETs the same? What mechanisms operate in cells that constitutively lack MPO (e.g., chicken heterophils)?
What is the fate of microbes trapped in NETs in vitro?
—Are organisms trapped and thereby immobilized for attack by other elements of the immune system—soluble and cellular?
—Are organisms killed in situ by NETs alone? If so, how? If killing is MPO-dependent, what are the sources of H2O2?
Are NETs generated in vivo during infection?
What is the contribution of NETs-mediated antimicrobial action to overall host defense?
—In the presence of intact phagocytes, what fraction of microbial killing or bacteriostasis can be attributed NETs?
—How do the signals that promote formation of NETs derail those that initiate events that promote apoptosis?
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