Malaria Sporozoites Traverse Host Cells within Transient Vacuoles

Risco-Castillo, Verónica; Topçu, Selma; Marinach, Carine; Manzoni, Giulia; Bigorgne, Amélie; Briquet, Sylvie; Baudin, Xavier; Lebrun, Maryse; Dubremetz, Jean‐François; Silvie, Olivier

doi:10.1016/j.chom.2015.10.006

Cited by 121 publications

(172 citation statements)

References 40 publications

Supporting

Mentioning

169

Contrasting

Order By: Relevance

“…They further validated this finding through microscopy studies showing LC3 deposition on the parasitophorous vacuole, and colocalization of parasites with Lysotracker red (LTR) stained acidic vesicles in response to IFN-γ stimulation. Notably, these results are in line with a study of the rodent parasite P. yoelii, which demonstrated that LTR-positive vesicles colocalized with sporozoites that failed to egress from their traversal vacuoles within hepatocytes (9).…”

supporting

confidence: 78%

IFN-γ protects hepatocytes againstPlasmodium vivaxinfection via LAP-like degradation of sporozoites

Lelliott

Coban

2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

supporting

confidence: 78%

IFN-γ protects hepatocytes againstPlasmodium vivaxinfection via LAP-like degradation of sporozoites

Lelliott

Coban

2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

“…Because we have codeveloped a humanized mouse model for P. vivax hypnozoite persistence (4), this question can now be further explored and will be a subject of our future study. Moreover, a recent study in P. yoelii by Risco-Castillo and colleagues (42) showed that parasites that fail to egress from their transient traversal vacuoles are colocalized with host lysosomes. Whether the LAP-like noncanonical autophagy process described here with P. vivax is involved in this process is of interest and may be a subject of further study.…”

Section: Liver-stage P Vivax Colocalizes With Lc3 and Ltrmentioning

confidence: 99%

LAP-like process as an immune mechanism downstream of IFN-γ in control of the human malariaPlasmodium vivaxliver stage

Boonhok

Rachaphaew

Duangmanee

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

IFN-γ is a major regulator of immune functions and has been shown to induce liver-stage Plasmodium elimination both in vitro and in vivo. The molecular mechanism responsible for the restriction of liver-stage Plasmodium downstream of IFN-γ remains uncertain, however. Autophagy, a newly described immune defense mechanism, was recently identified as a downstream pathway activated in response to IFN-γ in the control of intracellular infections. We thus hypothesized that the killing of liver-stage malarial parasites by IFN-γ involves autophagy induction. Our results show that whereas IFN-γ treatment of human hepatocytes activates autophagy, the IFN-γ-mediated restriction of liver-stage Plasmodium vivax depends only on the downstream autophagy-related proteins Beclin 1, PI3K, and ATG5, but not on the upstream autophagy-initiating protein ULK1. In addition, IFN-γ enhanced the recruitment of LC3 onto the parasitophorous vacuole membrane (PVM) and increased the colocalization of lysosomal vesicles with P. vivax compartments. Taken together, these data indicate that IFN-γ mediates the control of liver-stage P. vivax by inducing a noncanonical autophagy pathway resembling that of LC3-associated phagocytosis, in which direct decoration of the PVM with LC3 promotes the fusion of P. vivax compartments with lysosomes and subsequent killing of the pathogen. Understanding the hepatocyte response to IFN-γ during Plasmodium infection and the roles of autophagy-related proteins may provide an urgently needed alternative strategy for the elimination of this human malaria.autophagy | LC3-associated phagocytosis | IFN-γ | malaria S everal hundred million cases of human malaria are reported annually, and nearly 600,000 people die from the disease each year (1). Of the five species that infect humans, Plasmodium vivax is not only the most geographically widespread, but also the most prevalent malarial parasite in areas outside Africa. As such, it has caused massive morbidity in these regions of the world. Although malaria caused by P. vivax was previously regarded as benign compared with that caused by Plasmodium falciparum, the recent alarming increase in both the severity and the drug resistance of P. vivax infection has raised concern (2).The widespread distribution of P. vivax has been attributed to the parasite's ability to remain dormant in the liver for years before reactivation (3). The molecular mechanism responsible for P. vivax dormancy is unknown, and knowledge of Plasmodiumhepatocyte interactions remains very limited. Nonetheless, because the number of liver-stage parasites is in the range of 100, whereas in the blood stage as many as 10 13 organisms may be found (4), intervention at the liver stage would seem to offer a better strategy for parasite elimination. A prerequisite to this route of malaria control and the development of novel therapies is a better understanding of liver-stage Plasmodium and its interactions with host hepatocytes. IFN-γ was previously shown to exhibit antimalarial activity against the liver stag...

show abstract

“…All Apicomplexa have in common the sporozoite stage. Unlike blood stages, the sporozoite is an accessible extracellular stage, which is characterized by its motility and its ability to traverse cells (26)(27)(28) without forming a parasitophorous vacuole. Thus, this parasite stage has an opportunity to directly interact with host tRNAs.…”

Section: Significancementioning

confidence: 99%

Apicomplexa -specific tRip facilitates import of exogenous tRNAs into malaria parasites

Bour

Mahmoudi

Kapps

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The malaria-causing Plasmodium parasites are transmitted to vertebrates by mosquitoes. To support their growth and replication, these intracellular parasites, which belong to the phylum Apicomplexa, have developed mechanisms to exploit their hosts. These mechanisms include expropriation of small metabolites from infected host cells, such as purine nucleotides and amino acids. Heretofore, no evidence suggested that transfer RNAs (tRNAs) could also be exploited. We identified an unusual gene in Apicomplexa with a coding sequence for membrane-docking and structurespecific tRNA binding. This Apicomplexa protein-designated tRip (tRNA import protein)-is anchored to the parasite plasma membrane and directs import of exogenous tRNAs. In the absence of tRip, the fitness of the parasite stage that multiplies in the blood is significantly reduced, indicating that the parasite may need host tRNAs to sustain its own translation and/or as regulatory RNAs. Plasmodium is thus the first example, to our knowledge, of a cell importing exogenous tRNAs, suggesting a remarkable adaptation of this parasite to extend its reach into host cell biology.tRNA | Plasmodium | trafficking

show abstract

Malaria Sporozoites Traverse Host Cells within Transient Vacuoles

Cited by 121 publications

References 40 publications

IFN-γ protects hepatocytes againstPlasmodium vivaxinfection via LAP-like degradation of sporozoites

IFN-γ protects hepatocytes againstPlasmodium vivaxinfection via LAP-like degradation of sporozoites

LAP-like process as an immune mechanism downstream of IFN-γ in control of the human malariaPlasmodium vivaxliver stage

Apicomplexa -specific tRip facilitates import of exogenous tRNAs into malaria parasites

Contact Info

Product

Resources

About