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Antibody-independent mechanisms regulate the establishment of chronic Plasmodium infection
Thibaut Brugat1, Adam James Reid2, Jingwen Lin1
1The Francis Crick institute, London NW1 1AT, UK.
Abstract:
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 the 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: Plasmodium falciparum and Plasmodium knowlesi. Furthermore, little is understood about the early events in the establishment of chronic infection in these species. Using a rodent model we demonstrate that from the infecting population, only a minority of parasites, expressing one of several clusters of virulence-associated pir genes, establishes a chronic infection. This process occurs in different species of parasites and in different hosts. Establishment of chronicity is independent of adaptive immunity and therefore different from the mechanism proposed for maintenance 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. Because 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.
Insights
A minority of malaria parasites expressing specific virulence genes establish chronic infections, independent of host immunity. This process, regulated by pir gene expression, may be common across Plasmodium species.
Area of Science:
- Parasitology
- Immunology
- Infectious Diseases
Background:
- Malaria, caused by Plasmodium parasites, establishes chronic infections that sustain transmission.
- Antigenic variation is thought to maintain chronic infections, but the genes involved are known only for Plasmodium falciparum and Plasmodium knowlesi.
- Early events in chronic infection establishment remain poorly understood.
Purpose of the Study:
- To investigate the early events in the establishment of chronic malaria infections.
- To determine the role of virulence-associated pir genes in chronic infection.
- To explore whether this process is conserved across Plasmodium species.
Main Methods:
- Utilized a rodent model to study Plasmodium infection dynamics.
- Analyzed parasite populations to identify those establishing chronic infections.
- Investigated the expression of virulence-associated pir genes.
Main Results:
- Only a subset of infecting Plasmodium parasites, expressing specific pir gene clusters, establishes chronic infection.
- Establishment of chronicity is independent of adaptive immunity.
- The proportion of parasites expressing different pir gene types influences the time to establish chronic infection.
Conclusions:
- A minority population of parasites regulates chronic infection establishment through pir gene expression, independent of adaptive immunity.
- This mechanism may represent a conserved strategy for regulating chronic Plasmodium infections across species.
- Understanding pir gene regulation offers insights into malaria transmission dynamics.
