TY - JOUR
T1 - Innate and Adaptive Immunity to Transfused Allogeneic RBCs in Mice Requires MyD88
AU - Soldatenko, Arielle
AU - Hoyt, Laura R.
AU - Xu, Lan
AU - Calabro, Samuele
AU - Lewis, Steven M.
AU - Gallman, Antonia E.
AU - Hudson, Krystalyn E.
AU - Stowell, Sean R.
AU - Luckey, Chance J.
AU - Zimring, James C.
AU - Liu, Dong
AU - Santhanakrishnan, Manjula
AU - Hendrickson, Jeanne E.
AU - Eisenbarth, Stephanie C.
N1 - Funding Information:
This work was supported by National Institutes of Health Grant P01 HL132819 (to S.C.E.).
Publisher Copyright:
Copyright © 2022 by The American Association of Immunologists, Inc.
PY - 2022/2/15
Y1 - 2022/2/15
N2 - RBC transfusion therapy is essential for the treatment of anemia. A serious complication of transfusion is the development of non-ABO alloantibodies to polymorphic RBC Ags; yet, mechanisms of alloantibody formation remain unclear. Storage of mouse RBCs before transfusion increases RBC immunogenicity through an unknown mechanism. We previously reported that sterile, stored mouse RBCs activate splenic dendritic cells (DCs), which are required for alloimmunization. Here we transfused mice with allogeneic RBCs to test whether stored RBCs activate pattern recognition receptors (PRRs) on recipient DCs to induce adaptive immunity. TLRs are a class of PRRs that regulate DC activation, which signal through two adapter molecules: MyD88 and TRIF. We show that the inflammatory cytokine response, DC activation and migration, and the subsequent alloantibody response to transfused RBCs require MyD88 but not TRIF, suggesting that a restricted set of PRRs are responsible for sensing RBCs and triggering alloimmunization.
AB - RBC transfusion therapy is essential for the treatment of anemia. A serious complication of transfusion is the development of non-ABO alloantibodies to polymorphic RBC Ags; yet, mechanisms of alloantibody formation remain unclear. Storage of mouse RBCs before transfusion increases RBC immunogenicity through an unknown mechanism. We previously reported that sterile, stored mouse RBCs activate splenic dendritic cells (DCs), which are required for alloimmunization. Here we transfused mice with allogeneic RBCs to test whether stored RBCs activate pattern recognition receptors (PRRs) on recipient DCs to induce adaptive immunity. TLRs are a class of PRRs that regulate DC activation, which signal through two adapter molecules: MyD88 and TRIF. We show that the inflammatory cytokine response, DC activation and migration, and the subsequent alloantibody response to transfused RBCs require MyD88 but not TRIF, suggesting that a restricted set of PRRs are responsible for sensing RBCs and triggering alloimmunization.
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U2 - 10.4049/jimmunol.2100784
DO - 10.4049/jimmunol.2100784
M3 - Article
C2 - 35039331
AN - SCOPUS:85124056115
SN - 0022-1767
VL - 208
SP - 991
EP - 997
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -