TLR9 is required in donor blood for inflammation-induced immunization to an alloantigen on transfused RBCs in mice
5 affiliations
- 1Beirne Carter Immunology Center, University of Virginia
- 2Department of Pathology, University of Virginia
- 3Department of Pathology and Cell Biology, Columbia University
- 4Canadian Blood Services
- 5Department of Pathology and Laboratory Medicine, University of British Columbia
Abstract
Humoral immunization to alloantigens on transfused red blood cells (RBCs) remains a major barrier to safe and effective blood transfusion in chronically transfused patients. However, only some patients become alloimmunized following multiple transfusion. It was first observed in mice and then confirmed in humans that recipient inflammation at the time of transfusion increases rates of RBC alloimmunization. Viral double-stranded RNA has been extensively studied and shown to enhance alloimmunization through activation of recipient MAVS (mitochondrial antiviral-signaling protein) and subsequent induction of alpha-interferon. However, no one has reported testing the role of innate immune receptors on donor cells. Herein, we report that recipient exposure to another innate immune activator (CpG) enhances alloimmunization to transfused RBCs in a TLR9-dependent fashion. In addition, TLR9 is required both on the transfused donor cells and in the recipient. To the best of our knowledge, this is the first report of innate immune receptors on transfused donor cells regulating RBC alloimmunization. In addition to adding a new conceptual component to the mechanistic landscape of RBC alloimmunization, these findings raise the possibility of decreasing RBC alloimmunization either by selecting RBC units from donors with known hypomorphic TLR9 gene variants or by introducing TLR9 antagonists into donor blood.
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BibTeX
@article{jash2026tlr9,
title = {{TLR9 is required in donor blood for inflammation-induced immunization to an alloantigen on transfused RBCs in mice}},
author = {Arijita Jash and Krystalyn E. Hudson and James C. Zimring},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1952683},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1952683/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - TLR9 is required in donor blood for inflammation-induced immunization to an alloantigen on transfused RBCs in mice
AU - Arijita Jash
AU - Krystalyn E. Hudson
AU - James C. Zimring
PY - 2026
DA - 2026/10/26
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1952683
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1952683/full
AB - Humoral immunization to alloantigens on transfused red blood cells (RBCs) remains a major barrier to safe and effective blood transfusion in chronically transfused patients. However, only some patients become alloimmunized following multiple transfusion. It was first observed in mice and then confirmed in humans that recipient inflammation at the time of transfusion increases rates of RBC alloimmunization. Viral double-stranded RNA has been extensively studied and shown to enhance alloimmunization through activation of recipient MAVS (mitochondrial antiviral-signaling protein) and subsequent induction of alpha-interferon. However, no one has reported testing the role of innate immune receptors on donor cells. Herein, we report that recipient exposure to another innate immune activator (CpG) enhances alloimmunization to transfused RBCs in a TLR9-dependent fashion. In addition, TLR9 is required both on the transfused donor cells and in the recipient. To the best of our knowledge, this is the first report of innate immune receptors on transfused donor cells regulating RBC alloimmunization. In addition to adding a new conceptual component to the mechanistic landscape of RBC alloimmunization, these findings raise the possibility of decreasing RBC alloimmunization either by selecting RBC units from donors with known hypomorphic TLR9 gene variants or by introducing TLR9 antagonists into donor blood.
SN - 1664-3224
ER -