徳島大学 教育・研究者情報データベース(EDB)

1. 千田 淳司([徳島大学.先端酵素学研究所.基幹研究部門])

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2. 原 英之

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3. 内山 圭司

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4. 高橋 悦久([徳島大学.先端酵素学研究所.重点研究部門])

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5. (英) Miyata Hironori

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6. 小迫 英尊([徳島大学.先端酵素学研究所.基幹研究部門])

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7. (英) Tomioka Yukiko

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8. (英) Ito Toshihiro

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9. (英) Horiuchi Hiroyuki

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10. (英) Matsuda Haruo

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11. 木戸 博([徳島大学.先端酵素学研究所.重点研究部門])

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12. 坂口 末廣([徳島大学.先端酵素学研究所.基幹研究部門])

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(英) Prion protein signaling induces M2 macrophage polarization and protects from lethal influenza infection in mice.

(英) The cellular prion protein, PrPC, is a glycosylphosphatidylinositol anchored-membrane glycoprotein expressed most abundantly in neuronal and to a lesser extent in non-neuronal cells. Its conformational conversion into the amyloidogenic isoform in neurons is a key pathogenic event in prion diseases, including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. However, the normal functions of PrPC remain largely unknown, particularly in non-neuronal cells. Here we show that stimulation of PrPC with anti-PrP monoclonal antibodies (mAbs) protected mice from lethal infection with influenza A viruses (IAVs), with abundant accumulation of anti-inflammatory M2 macrophages with activated Src family kinases (SFKs) in infected lungs. A SFK inhibitor dasatinib inhibited M2 macrophage accumulation in IAV-infected lungs after treatment with anti-PrP mAbs and abolished the anti-PrP mAb-induced protective activity against lethal influenza infection in mice. We also show that stimulation of PrPC with anti-PrP mAbs induced M2 polarization in peritoneal macrophages through SFK activation in vitro and in vivo. These results indicate that PrPC could activate SFK in macrophages and induce macrophage polarization to an anti-inflammatory M2 phenotype after stimulation with anti-PrP mAbs, thereby eliciting protective activity against lethal infection with IAVs in mice after treatment with anti-PrP mAbs. These results also highlight PrPC as a novel therapeutic target for IAV infection.

1. (英) Article.ELocationID: 10.1371/journal.ppat.1008823

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) CoiStatement: The authors have declared that no competing interests exist.