Erythroid progenitors sense and respond to viral infection via nucleic acid sensors

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B981
Abstract ID: 4337

Presenting Author:
Rebecca L Clements , Visiting Assistant Professor at Swarthmore Col., Univ. of Pennsylvania Perelman Sch. of Med.

Abstract:

Red blood cells (RBCs) are not typically considered to be active mediators of immunity. This dogma stems from the fact that RBC precursors discard their organelles as they mature, thus losing the ability to alter gene expression in response to stimuli. Intriguingly, nucleated erythroid progenitors (nRBCs) circulate in healthy human fetuses and neonates, as well as adults with chronic or severe illnesses. There is limited evidence that nRBCs are immunomodulatory, yet our knowledge of underlying mechanisms remains inadequate. To define the role of human nRBCs, we queried single cell RNA-seq data and found that transcriptomics support nRBCs as putative immune mediators.

Unexpectedly, we found that nRBCs express nucleic acid-sensing pattern recognition receptors. Given the important role of nucleic acid sensors in detecting and responding to viral infection, we aimed to investigate the antiviral response of nRBCs in the presence of viral mimetics (poly I:C and cytosolic DNA). Using bulk RNA-seq analysis, we find that viral mimetics induce transcription of interferon-stimulated genes in human nRBCs. These data suggest a putative functionality for nRBCs in mediating innate antiviral immunity.

Our findings shed light on a unique orchestrator of immunity that is present during human development and times of stress. These experiments provide valuable insight into the mechanisms that erythroid cells utilize to contribute to host defense.