Persistent bone marrow hemozoin accumulation confers a survival advantage against bacterial infection via cell-intrinsic Myd88 signaling

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 my...

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Veröffentlicht in:Cell reports (Cambridge) 2024-10, Vol.43 (10), p.114850, Article 114850
Hauptverfasser: Zhu, Yanhui, Gao, Qingxiang, Zhang, Jia, Cheng, Yu, Yang, Shuzhen, Xu, Ren, Yuan, Jing, Novakovic, Boris, Netea, Mihai G., Cheng, Shih-Chin
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Sprache:eng
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Zusammenfassung: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. [Display omitted] •Hemozoin (Hz) drives myelopoiesis via cell-intrinsic MyD88 signaling•P. yoelli (Py) infection enhances bacterial survival through boosted myelopoiesis•Monocytes from Py-infected mice show elevated ROS production upon stimulation•Hz alters bone marrow progenitors, bolstering immunity after malaria infection Zhu et al. report that hemozoin deposition in the bone marrow following Plasmodium infection induces a sustained myelopoiesis bias through a MyD88-dependent mechanism. This reprogramming results in monocytes producing increased reactive oxygen species, while the myelopoiesis bias enhances cytokine production, supporting emergency myelopoiesis and, ultimately, boosting antibacterial capacity.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2024.114850