IgA-virus immune complexes potentiate netosis in neutrophils, leading to higher levels of netosis compared to antibody alone or virus alone.
Monoclonal antibodies that bind the stalk region of the influenza virus hemagglutinin can induce netosis in neutrophils, suggesting potential protection against influenza.
Neutrophil extracellular traps (NETs) can physically trap influenza virus particles, but further research is needed to determine their antiviral activity.
Deep dives
IGA-mediated netosis is stimulated by influenza virus
When monomeric IGA antibodies are complexed with influenza virus, it induces higher levels of netosis in neutrophils compared to antibody alone or virus alone. This stimulation is specific to IGA, as IGG does not induce netosis in the presence of the virus. The stimulation is more efficient when the ratio of IGA to virus is two to one. Pictures show the formation of nets, consisting of DNA strands and neutrophil elastase, in the presence of IGA and influenza virus.
Broadly neutralizing antibodies that bind the stalk of influenza virus induce netosis
Monoclonal antibodies that bind the stalk of the influenza virus hemagglutinin induce netosis in neutrophils, while antibodies that bind the head region do not. This suggests that the interaction of the Fc portion of the antibody with the neutrophil, combined with the binding of the viral head to sialic acid receptors on nearby neutrophils, can stimulate netosis. Antibodies that bind the stalk region may provide additional protection against influenza by promoting netosis.
Nets can trap viruses but may not inactivate them completely
Neutrophil extracellular traps (NETs) can physically trap influenza virus particles. However, it is unclear if the trapped viruses are completely inactivated. The reduction in infectivity observed when measuring percent infectivity may not be biologically significant, as it does not demonstrate a sufficient level of inactivation. Further research is needed to determine the fate of trapped viruses in vivo and to evaluate the potential antiviral activity of NETs.
Linking NLRP3 inflammasome to obesity and insulin resistance
There is evidence of an association between NLRP3 inflammasome, obesity, and insulin resistance. Obesity and diabetes have been linked to vascular endothelial dysfunction and pro-inflammatory states, which can affect the NLRP3 inflammasome and tissue factor expression. While obtaining a biomarker profile specifically for NLRP3 expression is challenging due to its cytosolic location, exploring associated SNPs or assessing response to stimulation could offer insights.
Complement as a key topic of discussion and invitation for a complement expert
Complement systems and their complexities are often difficult to understand, but their role in immunity is crucial. It may be helpful to invite complement experts like Claudia Kemper at NIH and John Lambert at the University of Pennsylvania to discuss complement in more detail, including its relevance in technology and therapeutics.
The immune professors discuss neutrophil extracellular traps, and how IgA-virus immune complexes potentiate this process through Fc receptors on neutrophils.
