13 November 2021

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.


  1. Fascinating. I assume this is at least partly responsible for "anemia of chronic disease." I never found explanations for the etiology of this to be particularly satisfying.

  2. try putting it though https://sci-hub.se/ to get through the paywall

    1. I tried, but got this:

      статья не найдена в базе

      (a Cyrillic 404)

  3. Hunted out of Sweden! Sci Hub is open for biz here:
    https://sci-hub.mksa.top/ . . . until tea-time or the Elsevier Swat Team abseils in through the window.
    But here's the thing. Humans have 10 TLRs, all presumably [equally?] useful in our immune system, but science funding follows success rather than explores actual new frontiers so TLR4 attracts 10x the attention as TLR5. This finding may give a boost to the TLR9ers and help them find gold.
    TLR Papers Reviews
    TLR4 10116 633
    TLR5 882 44
    TLR7 1689 145
    TLR9 3070 274

    1. "Sorry, sci-hub has not included this article yet..."


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