天美传媒

Abstract

According to clinical data, patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at risk for infection and severe sepsis, both of which significantly impact the transplant’s success. This suggests that the inflammatory immune response is dysregulated in this clinical setting. Here, by utilizing a mouse model of haploidentical bone marrow transplantation (haplo-BMT), we found that uncontrolled macrophage irritation underlies the pathogenesis of the two LPS-and E.coli-prompted sepsis in beneficiary creatures with join versus-have illness (GVHD). Macrophage-induced inflammation was mechanistically dependent on MMP9-mediated activation of TGF- 1 when neutrophil maturation was deficient in GVHD mice following haplo-BMT. Consequently, post-haplo-BMT, adoptive transfer of mature neutrophils purified from wild-type donor mice prevented infectious as well as sterile sepsis in GVHD mice. Together, our discoveries distinguish an original mature neutrophil-subordinate guideline of macrophage fiery reaction in a haplo-BMT setting and give valuable insights for creating clinical procedures for patients experiencing post-HSCT sepsis.