Research From Past NBF Grant Recipient Shows That Red Blood Cells Activate Innate Immune System

Nilam Mangalmurti, MD, a 2011 National Blood Foundation early-career Scientific Research Grant recipient, recently published research demonstrating that red blood cells are essential components of inflammatory responses in mammals. The findings were published last week in Science Translational Medicine.

In the study, Mangalmurti and her colleagues showed that RBCs alert the immune system to the presence of bacteria, parasites and circulating cell-free mitochondrial DNA through surface expression of the nucleic acid–sensing Toll-like receptor 9 (TLR9). In addition, they found that RBC-bound DNA was enriched in humans and mice during sepsis, driving erythrophagocytosis by splenic macrophages and resulting in acute anemia. The authors also demonstrated that RBC-bound mitochondrial DNA was enriched in the peripheral blood of patients with viral pneumonia or sepsis related to COVID-19 compared to patients who had COVID-19 without viral pneumonia or sepsis.

Mangalmurti and her colleagues suggest that targeting RBC-TLR9 with blocking antibodies or antagonistic small-molecule inhibitors may be a viable option to combat inflammatory anemia. They posit that this could potentially eliminate the enhanced CpG-TLR9–mediated RBC phagocytosis without interfering with CpG-TLR9 signaling in classical immune cells essential for host defense.

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