Inhibition of dendritic cell development via the suppression of transcription factor IRF8 by malaria

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08764
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Yokohama City University
• Principal Investigator: ICHINO Motohide 横浜市立大学, 医学部, 助教 (60271368)
• Research Collaborator: TAMURA Tomohiko ; Nishiyama Akira ; NAKABAYASHI Jun
• Project Period (FY): 2016-10-21 – 2019-03-31
• Keywords: マラリア / 樹状細胞 / IRF8 / 免疫抑制

Outline of Final Research Achievements

Malaria parasites suppress host immune responses during its infection to evade host immunity. To understand the molecular and cellular mechanisms of the suppression of dendritic cell (DC) development, we analysed DC subsets in the spleen of malaria parasite-infected mice. We found that the reduced ratio of cDC1 subset in the spleen of the parasite-infected mice accompanied by the decreased expression of transcription factor IRF8 compared with the spleen cells in the uninfected mice. Also, we found that the bone marrow cells cultured with the parasite-infected red blood cells in vitro developed fewer amount of cDC1. Especially, few splenic XCR1+ DCs were detected in the parasite-infected mice. These results suggest that malaria parasites inhibit the development of XCR1+ DCs, suppressing the expression of IRF8 during infection.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

マラリアは死者数の最も多い寄生虫感染症である。ノーベル賞を受賞した抗マラリア薬に対してすら薬剤耐性原虫の出現が問題となっており、開発されたワクチンも残念ながら効果は限定的である。本研究は、マラリア原虫による免疫抑制に着目し、免疫抑制のメカニズムを明らかにすることを目的とする。免疫細胞の中でもとくに重要な樹状細胞の分化機能不全でマラリアをとらえる視点が新しく、新しい治療法開発につなげるために、免疫抑制を解除して防御的な免疫応答誘導を目指すものである。