IgA-virus Immune Complex: Neutrophil’s trap for SARS-CoV-2

Kanikah Mehndiratta, MSc, University of Glasgow

IgA stimulated neutrophil spider-webs have been explored a lot in the past few years for their antiviral mechanisms. These antibodies in particular are one of the most abundant in the immune system, richly present on mucosal surfaces and involved in the body’s defence mechanism against viral infections. During the whole COVID-19 pandemic, which is becoming deadlier by the day, a lot of research is going into how the immune systems of certain patients aided in their survival with a quicker response and least severity. Understanding the defence mechanism in the respiratory system by the immune cells involved in the antiviral response against the SARS-CoV-2 virus strains could help in the potential development of more effective vaccines.

IgA antibodies mediated extracellular traps against viruses

Antibodies usually act by directly neutralizing viruses, but they can also be immuno-pathogenic by interacting with certain specific Fc receptors, presenting at various immune-cell subtypes such as neutrophils. The antiviral properties of IgG-virus immune complexes have been researched well enough but the mechanism of apoptosis in neutrophils by an IgA-virus immune complex resulting in antiviral effector proteins is still unclear. A 2021 study conducted by Emory university tries to explain the immuno-pathogenic mechanism of such proteins in killing the CoV-2 virus strains in some while the same proteins in elevating respiratory failure associated symptoms in other patients leading to death.

NETs targeting SARS-CoV-2

Neutrophils are the most plentiful type of WBCs in the human body and are usually very effective in their defence strategies against microbial infections. They bear Fc alpha receptors on their surface, present on many other immune cells too, that interact with the immune complex between the IgA and the CoV-2 virus (ICs). The study explains the stimulation of such neutrophils through this interaction leading to an apoptotic mechanism called NETosis. This involves neutrophil explosion and release of neutrophil extracellular traps (NETs) which encompass their chromatin material studded with antiviral effector proteins. These spider webs can effectively trap and inactivate the pathogenic viral strains, here SARS-CoV-2 and form an IgA-virus immune complex. But the specific histone and granule proteins in NETs, neutrophil elastase and myeloperoxidase can also unintentionally contribute to the pathophysiology of respiratory infections as the associated traps can cause lung damage, fibrosis and pulmonary embolism. Various studies have reported the presence of NETs in COVID-19 injured lungs of dead patients. They are even being called potential COVID-19 drivers and the leading cause of symptom severity.

Conclusion:

Poor regulation of NETs that are intended by the body’s immune system to eliminate the SARS-CoV-2 infection, sometimes actually results in a fatality, and more research into their antiviral activity is essential for targeting the deadly disease. The research would also help in creating future, more effective COVID-19 vaccines based on ICs apoptotic neutrophil mechanisms. These could be administered orally or through nasal sprays, instead of needles, making them a great candidate to deal with the current hectic vaccination drives around the world. This could also reduce the overwhelming strain of the pandemic on healthcare worldwide. The whole study also emphasizes the need for better research into immuno-pathogenic side effects of such NETs in individual patients.

Also read: Phenotypic Imaging of Nephroblastoma Cancer cells

References:

1. Stacey, H. D., Golubeva, D., Posca, A., Ang, J. C., Novakowski, K. E., Zahoor, M. A., Kaushic, C., Cairns, E., Bowdish, D. M. E., Mullarkey, C. E., & Miller, M. S. (2021). IgA potentiates NETosis in response to viral infection. Proceedings of the National Academy of Sciences, 118(27), e2101497118. https://doi.org/10.1073/pnas.2101497118
2. Radermecker, C., Detrembleur, N., Guiot, J., Cavalier, E., Henket, M., d’Emal, C., Vanwinge, C., Cataldo, D., Oury, C., Delvenne, P., & Marichal, T. (2020). Neutrophil extracellular traps infiltrate the lung airway, interstitial, and vascular compartments in severe COVID-19. Journal of Experimental Medicine, 217(12), e20201012. https://doi.org/10.1084/jem.20201012

About author:

Kanikah Mehndiratta is an avid researcher in the field of Genetics with a background in Biotechnology. She is a post-graduate from University of Glasgow in their Medical Genetics and Genomics program. Currently, based in Chandigarh as a Scientific Writer, she involves herself mainly in projects related to neurological disorders. Outside of academics, she likes to read novels, travel, and is involved in volunteer work mostly.

LinkedIn profile- https://www.linkedin.com/in/kanikah-mehndiratta-301830171

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