Antibody-independent mechanisms regulate the establishment of chronic Plasmodium infection

Thibaut Brugat, Adam James Reid, Jingwen Lin, Deirdre Cunningham, Irene Tumwine, Garikai Kushinga, Sarah McLaughlin, Philip Spence, Ulrike Böhme, Mandy Sanders, Solomon Conteh, Ellen Bushell, Tom Metcalf, Oliver Billker, Patrick E. Duffy, Chris I Newbold, Matthew Berriman, Jean Langhorne

Research output: Contribution to journalArticlepeer-review


Malaria is caused by parasites of the genus Plasmodium. All human-infecting Plasmodium species can establish long-lasting chronic infections1-5, creating an infectious reservoir to sustain transmission1,6. It is widely accepted that maintenance of chronic infection involves evasion of adaptive immunity by antigenic variation7. However, genes involved in this process have been identified in only two of five human-infecting species: P. falciparum and P. knowlesi. Furthermore, little is understood about the early events in establishment of chronic infection in these species. Using a rodent model we demonstrate that only a minority of parasites from among the infecting population, expressing one of several clusters of virulence associated pir genes, establishes a chronic infection. This process occurs in different species of parasite and in different hosts. Establishment of chronicity is independent of adaptive immunity and therefore different from the mechanism proposed for maintainance of chronic P. falciparum infections7-9. Furthermore, we show that the proportions of parasites expressing different types of pir genes regulate the time taken to establish a chronic infection. Since pir genes are common to most, if not all, species of Plasmodium10, this process may be a common way of regulating the establishment of chronic infections.
Original languageEnglish
Article number16276
Number of pages9
JournalNature Microbiology
Publication statusPublished - 6 Feb 2017

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