IgA potentiates NETosis in response to viral infection

Proc Natl Acad Sci U S A. 2021 Jul 6;118(27):e2101497118. doi: 10.1073/pnas.2101497118.


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.

Keywords: NETosis; SARS-CoV-2; influenza; neutrophils; viruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphainfluenzavirus / immunology
  • Antigen-Antibody Complex / immunology
  • Antigens, CD / metabolism
  • Extracellular Traps / immunology*
  • Extracellular Traps / virology
  • Humans
  • Immunoglobulin A / immunology*
  • NADPH Oxidases / metabolism
  • Neutrophils / immunology*
  • Neutrophils / pathology
  • Neutrophils / virology
  • Receptors, Fc / metabolism
  • SARS-CoV-2 / immunology
  • Signal Transduction
  • Virion
  • Virus Diseases / immunology*


  • Antigen-Antibody Complex
  • Antigens, CD
  • Fc(alpha) receptor
  • Immunoglobulin A
  • Receptors, Fc
  • NADPH Oxidases