Goswami Debashree, Kumar Sudhir, Betz William, Armstrong Janna M, Haile Meseret T, Camargo Nelly, Parthiban Chaitra, Seilie Annette M, Murphy Sean C, Vaughan Ashley M, Kappe Stefan H I
Center for Global Infectious Disease Research, Seattle Children's Research Institute, 307 Westlake Avenue N, Seattle, WA, USA.
Department of Laboratory Medicine and Pathology and Department of Microbiology, University of Washington, Seattle, WA, USA.
iScience. 2022 Apr 8;25(5):104224. doi: 10.1016/j.isci.2022.104224. eCollection 2022 May 20.
sporozoites invade hepatocytes and transform into liver stages within a parasitophorous vacuole (PV). The parasites then grow and replicate their genome to form exoerythrocytic merozoites that infect red blood cells. We report that the human malaria parasite expresses a C-type ATP-binding cassette transporter, ABCC2, which marks the transition from invasive sporozoite to intrahepatocytic early liver stage. Using a humanized mouse infection model, we show that ABCC2 localizes to the parasite plasma membrane in early and mid-liver stage parasites but is not detectable in late liver stages. sporozoites invade hepatocytes, form a PV, and transform into liver stage trophozoites but cannot transition to exoerythrocytic schizogony and fail to transition to blood stage infection. Thus, ABCC2 is an expression marker for early phases of parasite liver infection and plays an essential role in the successful initiation of liver stage replication.
子孢子侵入肝细胞并在寄生泡(PV)内转变为肝期。然后,寄生虫生长并复制其基因组,形成感染红细胞的红细胞外期裂殖子。我们报告说,人类疟原虫表达一种C型ATP结合盒转运蛋白ABCC2,它标志着从侵入性子孢子到肝内早期肝期的转变。使用人源化小鼠感染模型,我们表明ABCC2定位于肝期早期和中期寄生虫的寄生虫质膜,但在肝期晚期无法检测到。子孢子侵入肝细胞,形成PV,并转变为肝期滋养体,但无法转变为红细胞外裂体增殖,也无法转变为血期感染。因此,ABCC2是寄生虫肝感染早期阶段的表达标志物,在肝期复制的成功起始中起重要作用。