The immune function of red blood cells

That's a post title I could not have imagined writing back in the twentieth century, when everyone believed that RBCs were basically simple inert bags of hemoglobin.  We knew they had complement receptors and could be subject to immune attack, but not that they could serve a beneficial immuoregulatory function.  Now...

New research has revealed that red blood cells function as critical immune sensors by binding cell-free DNA, called nucleic acid, present in the body’s circulation during sepsis and COVID-19, and that this DNA-binding capability triggers their removal from circulation, driving inflammation and anemia during severe illness and playing a much larger role in the immune system than previously thought. 

Toll-like receptors (TLRs) are a class of proteins that play a key role in the immune system by activating immune responses like cytokine production. This study examined the red blood cells of about 50 sepsis patients and 100 COVID-19 patients and found that, during these illnesses, red blood cells express an increased amount of the specific TLR protein called TLR9 on their surface.

Basically, the circulating erythrocytes scavenge free DNA released into the bloodstream during cell injury and death.  Getting that material out of the blood is good for the host, but when the RBC gets coated with the scavenged DNA, it becomes subject to removal by macrophages in the spleen, leading to anemia.

I wasn't able to access the Science Translational Medicine source article.