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Persistent bone marrow hemozoin accumulation confers a survival advantage against bacterial infection via cell-intrinsic Myd88 signaling.
- Source :
-
Cell reports [Cell Rep] 2024 Oct 22; Vol. 43 (10), pp. 114850. Date of Electronic Publication: 2024 Oct 10. - Publication Year :
- 2024
-
Abstract
- Malaria remains a global health challenge, affecting millions annually. Hemozoin (Hz) deposition in the bone marrow disrupts hematopoiesis and modulates immune responses, but the mechanisms are not fully understood. Here, we show that persistent hemozoin deposition induces a sustained bias toward myelopoiesis, increasing peripheral myeloid cell numbers. Hz drives this process through a cell-intrinsic, MyD88-dependent pathway, enhancing chromatin accessibility of transcription factors such as Runx1 and Etv6 in granulocyte-macrophage progenitors. These findings are confirmed by intraosseous Hz injections and bone marrow chimeras. Single-cell RNA sequencing reveals increased reactive oxygen species production in monocytes from malaria-recovered mice, correlating with enhanced bactericidal capacity. This highlights an alternative aspect of post-malarial immunity and extends our understanding of trained immunity, suggesting that pathogen by-products like Hz can induce innate immune memory. These results offer insights into therapeutic strategies that harness trained immunity to combat infectious diseases.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Mice
Bacterial Infections immunology
Bacterial Infections metabolism
Reactive Oxygen Species metabolism
Malaria immunology
Malaria metabolism
Malaria parasitology
Myelopoiesis
Repressor Proteins metabolism
Immunity, Innate
Myeloid Differentiation Factor 88 metabolism
Signal Transduction
Core Binding Factor Alpha 2 Subunit metabolism
Bone Marrow metabolism
Mice, Inbred C57BL
Hemeproteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 43
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 39392758
- Full Text :
- https://doi.org/10.1016/j.celrep.2024.114850