Lipopolysaccharide preconditioning augments phagocytosis of malaria-parasitized red blood cells through induced bone marrow-derived macrophages in the liver, thereby increasing the murine survival after<i>Plasmodium yoelii</i>infection
Abstract Malaria remains a grave concern for humans, as effective medical countermeasures for malaria infection have yet to be developed. Phagocytic clearance of parasitized red blood cells (pRBCs) by macrophages is an important front-line innate host defense against malaria infection. We previously showed that repeated injections of low-dose lipopolysaccharide (LPS) prior to bacterial infection, called LPS preconditioning, strongly augmented phagocytic/bactericidal activity in murine macrophages. However, how LPS preconditioning prevents murine malaria infection is unclear. We investigated the protective effects of LPS preconditioning against lethal murine malaria infection, focusing on CD11bhighF4/80lowliver macrophages, which are increased by LPS preconditioning. Mice were subjected to LPS preconditioning by intraperitoneal injections of low-dose LPS for 3 consecutive days, and 24 h later, they were intravenously infected with pRBCs ofPlasmodium yoelii17XL. LPS preconditioning markedly increased the murine survival and reduced parasitemia, while it did not reduce TNF secretions, only delaying the peak of plasma IFN-γ after malaria infection in mice. Anin vitrophagocytic clearance assay of pRBCs showed that the CD11bhighF4/80lowliver macrophages of the LPS-preconditioned mice had significantly augmented phagocytic activity against pRBCs. The adoptive transfer of CD11bhighF4/80lowliver macrophages from LPS-preconditioned mice to control mice significantly improved the survival after malaria infection. We conclude that LPS preconditioning stimulated CD11bhighF4/80lowliver macrophages to augment the phagocytic clearance of pRBCs, which may play a central role in resistance against malaria infection. LPS preconditioning may be an effective tool for preventing malaria infection..
Medienart: |
Preprint |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
bioRxiv.org - (2023) vom: 01. Okt. Zur Gesamtaufnahme - year:2023 |
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Sprache: |
Englisch |
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Beteiligte Personen: |
Ono, Takeshi [VerfasserIn] |
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Links: |
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Themen: |
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doi: |
10.1101/2020.05.22.111765 |
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funding: |
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PPN (Katalog-ID): |
XBI01793057X |
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245 | 1 | 0 | |a Lipopolysaccharide preconditioning augments phagocytosis of malaria-parasitized red blood cells through induced bone marrow-derived macrophages in the liver, thereby increasing the murine survival after<i>Plasmodium yoelii</i>infection |
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520 | |a Abstract Malaria remains a grave concern for humans, as effective medical countermeasures for malaria infection have yet to be developed. Phagocytic clearance of parasitized red blood cells (pRBCs) by macrophages is an important front-line innate host defense against malaria infection. We previously showed that repeated injections of low-dose lipopolysaccharide (LPS) prior to bacterial infection, called LPS preconditioning, strongly augmented phagocytic/bactericidal activity in murine macrophages. However, how LPS preconditioning prevents murine malaria infection is unclear. We investigated the protective effects of LPS preconditioning against lethal murine malaria infection, focusing on CD11bhighF4/80lowliver macrophages, which are increased by LPS preconditioning. Mice were subjected to LPS preconditioning by intraperitoneal injections of low-dose LPS for 3 consecutive days, and 24 h later, they were intravenously infected with pRBCs ofPlasmodium yoelii17XL. LPS preconditioning markedly increased the murine survival and reduced parasitemia, while it did not reduce TNF secretions, only delaying the peak of plasma IFN-γ after malaria infection in mice. Anin vitrophagocytic clearance assay of pRBCs showed that the CD11bhighF4/80lowliver macrophages of the LPS-preconditioned mice had significantly augmented phagocytic activity against pRBCs. The adoptive transfer of CD11bhighF4/80lowliver macrophages from LPS-preconditioned mice to control mice significantly improved the survival after malaria infection. We conclude that LPS preconditioning stimulated CD11bhighF4/80lowliver macrophages to augment the phagocytic clearance of pRBCs, which may play a central role in resistance against malaria infection. LPS preconditioning may be an effective tool for preventing malaria infection. | ||
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700 | 1 | |a Nakashima, Masahiro |4 aut | |
700 | 1 | |a Ishikiriyama, Takuya |4 aut | |
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700 | 1 | |a Kinoshita, Manabu |4 aut | |
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