Vector transmission regulates immune control of Plasmodium virulence

Philip J. Spence, William Jarra, Prisca Levy, Adam J. Reid, Lia Chappell, Thibaut Brugat, Mandy Sanders, Matthew Berriman, Jean Langhorne*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Defining mechanisms by which Plasmodium virulence is regulated is central to understanding the pathogenesis of human malaria. Serial blood passage of Plasmodium through rodents(1-3), primates(4) or humans(5) increases parasite virulence, suggesting that vector transmission regulates Plasmodium virulence within the mammalian host. In agreement, disease severity can be modified by vector transmission(6-8), which is assumed to 'reset' Plasmodium to its original character(3). However, direct evidence that vector transmission regulates Plasmodium virulence is lacking. Here we use mosquito transmission of serially blood passaged (SBP) Plasmodium chabaudi chabaudi(9) to interrogate regulation of parasite virulence. Analysis of SBP P.c. chabaudi before and after mosquito transmission demonstrates that vector transmission intrinsically modifies the asexual blood-stage parasite, which in turn modifies the elicited mammalian immune response, which in turn attenuates parasite growth and associated pathology. Attenuated parasite virulence associates with modified expression of the pir multi-gene family. Vector transmission of Plasmodium therefore regulates gene expression of probable variant antigens in the erythrocytic cycle, modifies the elicited mammalian immune response, and thus regulates parasite virulence. These results place the mosquito at the centre of our efforts to dissect mechanisms of protective immunity to malaria for the development of an effective vaccine.

Original languageEnglish
Pages (from-to)228-231
JournalNature
Volume498
Issue number7453
DOIs
Publication statusPublished - 13 Jun 2013

Keywords

  • MOSQUITO-TRANSMISSION
  • RODENT MALARIA
  • EXPRESSION ANALYSIS
  • ANTIGENIC VARIANTS
  • CHABAUDI-CHABAUDI
  • MULTIGENE FAMILY
  • FALCIPARUM
  • INFECTIONS
  • DIVERSITY
  • PARASITES

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