2019年8月1日
CXCR4 regulates Plasmodium development in mouse and human hepatocytes
Journal of Experimental Medicine
- 巻
- 216
- 号
- 8
- 開始ページ
- 1733
- 終了ページ
- 1748
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1084/jem.20182227
The liver stage of the etiological agent of malaria, Plasmodium, is obligatory for successful infection of its various mammalian hosts. Differentiation of the rod-shaped sporozoites of Plasmodium into spherical exoerythrocytic forms (EEFs) via bulbous expansion is essential for parasite development in the liver. However, little is known about the host factors regulating the morphological transformation of Plasmodium sporozoites in this organ. Here, we show that sporozoite differentiation into EEFs in the liver involves protein kinase C ζ–mediated NF-κB activation, which robustly induces the expression of C-X-C chemokine receptor type 4 (CXCR4) in hepatocytes and subsequently elevates intracellular Ca levels, thereby triggering sporozoite transformation into EEFs. Blocking CXCR4 expression by genetic or pharmacological intervention profoundly inhibited the liver-stage development of the Plasmodium berghei rodent malaria parasite and the human Plasmodium falciparum parasite. Collectively, our experiments show that CXCR4 is a key host factor for Plasmodium development in the liver, and CXCR4 warrants further investigation for malaria prophylaxis. 2+
- リンク情報
-
- DOI
- https://doi.org/10.1084/jem.20182227
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/31189656
- PubMed Central
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683982
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85071068702&origin=inward 本文へのリンクあり
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85071068702&origin=inward
- ID情報
-
- DOI : 10.1084/jem.20182227
- ISSN : 0022-1007
- eISSN : 1540-9538
- PubMed ID : 31189656
- PubMed Central 記事ID : PMC6683982
- SCOPUS ID : 85071068702