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 CD11b^high F4/80^low liver 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 of Plasmodium yoelii 17XL. 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. An in vitro phagocytic clearance assay of pRBCs showed that the CD11b^high F4/80^low liver macrophages of the LPS-preconditioned mice had significantly augmented phagocytic activity against pRBCs. The adoptive transfer of CD11b^high F4/80^low liver macrophages from LPS-preconditioned mice to control mice significantly improved the survival after malaria infection. We conclude that LPS preconditioning stimulated CD11b^high F4/80^low liver 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.

中文翻译：

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脂多糖预处理通过诱导肝脏中骨髓衍生的巨噬细胞来增强疟疾寄生虫的红细胞的吞噬作用，从而提高约氏疟原虫感染后鼠的存活率

由于尚未开发出有效的针对疟疾感染的医学对策，疟疾仍然是人类的严重关切。巨噬细胞对寄生虫红细胞（pRBC）的吞噬清除作用是对抗疟疾感染的重要一线先天宿主防御。我们以前表明，在细菌感染之前反复注射低剂量脂多糖（LPS），称为LPS预处理，可大大增强鼠巨噬细胞的吞噬/杀菌活性。但是，LPS预处理如何预防鼠类疟疾感染尚不清楚。我们研究了LPS预处理对致命鼠类疟疾感染的保护作用，重点是CD11b^高F4 / 80^低肝脏巨噬细胞，可通过LPS预处理增加。通过连续3天腹膜内注射小剂量LPS​​对小鼠进行LPS预处理，然后在24小时后，用约氏疟原虫17XL的pRBC静脉感染它们。LPS预处理显着提高了鼠的存活率并降低了寄生虫血症，但并未降低TNF的分泌，仅延迟了小鼠感染疟疾后血浆IFN-γ的峰值。pRBC的体外吞噬清除试验表明，LPS预处理小鼠的CD11b^高F4 / 80^低肝巨噬细胞对pRBC的吞噬活性显着增强。过继转让CD11b^高F4 / 80^低从LPS预处理小鼠到对照小鼠的肝巨噬细胞可显着提高疟疾感染后的存活率。我们得出的结论是，LPS预处理刺激CD11b^高F4 / 80^低肝巨噬细胞，以增强pRBC的吞噬清除，这可能在抵抗疟疾感染中发挥重要作用。LPS预处理可能是预防疟疾感染的有效工具。