Malaria Sporozoites Traverse Host Cells within Transient Vacuoles

•Malaria sporozoites actively invade host cells inside two different types of vacuoles•Plasmodium sporozoites form MJ-independent transient vacuoles during cell traversal•Sporozoite egress from transient vacuoles depends on PLP1 and is regulated by pH•Failure to egress results in parasite degradation by the host cell lysosomes

SummaryPlasmodium sporozoites are deposited in the host skin by Anopheles mosquitoes. The parasites migrate from the dermis to the liver, where they invade hepatocytes through a moving junction (MJ) to form a replicative parasitophorous vacuole (PV). Malaria sporozoites need to traverse cells during progression through host tissues, a process requiring parasite perforin-like protein 1 (PLP1). We find that sporozoites traverse cells inside transient vacuoles that precede PV formation. Sporozoites initially invade cells inside transient vacuoles by an active MJ-independent process that does not require vacuole membrane remodeling or release of parasite secretory organelles typically involved in invasion. Sporozoites use pH sensing and PLP1 to exit these vacuoles and avoid degradation by host lysosomes. Next, parasites enter the MJ-dependent PV, which has a different membrane composition, precluding lysosome fusion. The malaria parasite has thus evolved different strategies to evade host cell defense and establish an intracellular niche for replication.

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