Once considered to be passive oxygen carriers, erythroid cells are now recognized as dynamic modulators of immune responses. Erythroid progenitors and precursors, collectively known as CD71⁺ erythroid cells, can suppress innate and adaptive immune responses in neonates, in mothers during pregnancy, in chronic conditions such as cancer and autoimmunity, and during infection with viruses, including SARS-CoV-2 and HIV. Mature red blood cells engage pathogens directly, scavenge chemokines, cytokines and nucleic acids, and modulate immune functions through redox buffering and receptor-mediated interactions. The immune effects of red blood cells are highly context dependent, ranging from suppression to activation. This Review highlights the emerging field of erythroid-immune crosstalk and its translational potential in the settings of infection, cancer, pregnancy and chronic inflammatory conditions.
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