title: The rodent malaria liver stage survives in the rapamycin-induced autophagosome of infected Hepa1-6 cells.
abstract: It has been reported that non-selective autophagy of infected hepatocytes could facilitate the development of malaria in the liver stage, but the fate of parasites following selective autophagy of infected hepatocytes is still not very clear. Here, we confirmed that sporozoite infection can induce a selective autophagy-like process targeting EEFs (exo-erythrocytic forms) in Hepa1-6. Rapamycin treatment greatly enhanced this process in EEFs and non-selective autophagy of infected Hepa1-6 cells and enhanced the development of the malaria liver stage in vivo. Although rapamycin promoted the fusion of autophagosomes containing the malaria parasite with lysosomes, some parasites inside the autophagosome survived and replicated normally. Further study showed that the maturation of affected autolysosomes was greatly inhibited. Therefore, in addition to the previously described positive role of rapamycin-induced nonselective autophagy of hepatocytes, we provide evidence that the survival of EEFs in the autophagosome of the infected hepatocytes also contributes to rapamycin-enhanced development of the malaria liver stage, possibly due to the suppression of autolysosome maturation by EEFs. These data suggest that the inhibition of autolysosome maturation might be a novel escape strategy used by the malaria liver stage.
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, Chongqing, 400038, P. R. China.|Department of Microbiology, Third Military Medical University, Chongqing, 400038, P. R. China.
authors.forename: Chenghao
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, Chongqing, 400038, P. R. China.
authors.forename: Taiping
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, Chongqing, 400038, P. R. China.
authors.forename: Taoli
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, Chongqing, 400038, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, Chongqing, 400038, P. R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, Chongqing, 400038, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, Chongqing, 400038, P. R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Pathogenic Biology, Third Military Medical University, Chongqing, 400038, P. R. China.
authors.forename: Wenyue
authors.initials: W
authors.lastname: Xu
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000071182:Autophagosomes / Q000187:drug effects* / Q000378:metabolism / Q000469:parasitology; D001343:Autophagy / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000469:parasitology / Q000473:pathology; D045744:Cell Line, Tumor; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000469:parasitology; D006790:Host-Parasite Interactions / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D008113:Liver Neoplasms / Q000469:parasitology / Q000473:pathology; D008288:Malaria / Q000378:metabolism* / Q000469:parasitology; D051379:Mice; D010967:Plasmodium yoelii / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology*; D034101:Sporozoites / Q000235:genetics / Q000502:physiology
chemical_list: D000903:Antibiotics, Antineoplastic; D020123:Sirolimus