ACE2-containing defensosomes serve as decoys to inhibit SARS-CoV-2 infection

Krystal L. Ching, Maren de Vries, Juan Gago, Kristen Dancel-Manning, Joseph Sall, William J. Rice, Clea Barnett, Alireza Khodadadi-Jamayran, Aristotelis Tsirigos, Feng Xia Liang, Lorna E. Thorpe, Bo Shopsin, Leopoldo N. Segal, Meike Dittmann, Victor J. Torres, Ken Cadwell

Research output: Contribution to journalArticlepeer-review


AEUxtr:aPcelelalusleacrovnefisrimcltehsatoafllehneaddoisnogmlevaellosarirgeirne,perxeosesnotmedecso,rrmecetdlyia: te intercellular communication by transporting substrates with a variety of functions related to tissue homeostasis and disease. Their diagnostic and therapeutic potential has been recognized for diseases such as cancer in which signaling defects are prominent. However, it is unclear to what extent exosomes and their cargo inform the progression of infectious diseases. We recently defined a subset of exosomes termed defensosomes that are mobilized during bacterial infection in a manner dependent on autophagy proteins. Through incorporating protein receptors on their surface, defensosomes mediated host defense by binding and inhibiting pore-forming toxins secreted by bacterial pathogens. Given this capacity to serve as decoys that interfere with surface protein interactions, we investigated the role of defensosomes during infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of Coronavirus Disease 2019 (COVID-19). Consistent with a protective function, exosomes containing high levels of the viral receptor ACE2 in bronchoalveolar lavage fluid (BALF) from critically ill COVID-19 patients was associated with reduced intensive care unit (ICU) and hospitalization times. We found ACE2+ exosomes were induced by SARS-CoV-2 infection and activation of viral sensors in cell culture, which required the autophagy protein ATG16L1, defining these as defensosomes. We further demonstrate that ACE2+ defensosomes directly bind and block viral entry. These findings suggest that defensosomes may contribute to the antiviral response against SARS-CoV-2 and expand our knowledge on the regulation and effects of extracellular vesicles during infection.

Original languageEnglish (US)
Article numbere3001754
JournalPLoS biology
Issue number9
StatePublished - Sep 2022

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Agricultural and Biological Sciences


Dive into the research topics of 'ACE2-containing defensosomes serve as decoys to inhibit SARS-CoV-2 infection'. Together they form a unique fingerprint.

Cite this