IgA potentiates NETosis in response to viral infection.
Hannah D StaceyDiana GolubevaAlyssa PoscaJann C AngKyle E NovakowskiMuhammad Atif ZahoorCharu KaushicEwa CairnsDawn M E BowdishCaitlin E MullarkeyMatthew S MillerPublished in: Proceedings of the National Academy of Sciences of the United States of America (2021)
IgA is the second most abundant antibody present in circulation and is enriched at mucosal surfaces. As such, IgA plays a key role in protection against a variety of mucosal pathogens including viruses. In addition to neutralizing viruses directly, IgA can also stimulate Fc-dependent effector functions via engagement of Fc alpha receptors (Fc-αRI) expressed on the surface of certain immune effector cells. Neutrophils are the most abundant leukocyte, express Fc-αRI, and are often the first to respond to sites of injury and infection. Here, we describe a function for IgA-virus immune complexes (ICs) during viral infections. We show that IgA-virus ICs potentiate NETosis-the programmed cell-death pathway through which neutrophils release neutrophil extracellular traps (NETs). Mechanistically, IgA-virus ICs potentiated a suicidal NETosis pathway via engagement of Fc-αRI on neutrophils through a toll-like receptor-independent, NADPH oxidase complex-dependent pathway. NETs also were capable of trapping and inactivating viruses, consistent with an antiviral function.
Keyphrases
- toll like receptor
- social media
- inflammatory response
- dendritic cells
- nuclear factor
- regulatory t cells
- induced apoptosis
- sars cov
- cystic fibrosis
- multidrug resistant
- cell proliferation
- pseudomonas aeruginosa
- escherichia coli
- cell cycle arrest
- biofilm formation
- dengue virus
- gram negative
- pi k akt
- endoplasmic reticulum stress