Antibody-independent mechanisms regulate the establishment of chronic Plasmodium infection.
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.
The Francis Crick institute, London NW1 1AT, UK.
Thibaut
T
Brugat
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Adam James
AJ
Reid
The Francis Crick institute, London NW1 1AT, UK.
Jingwen
J
Lin
The Francis Crick institute, London NW1 1AT, UK.
Deirdre
D
Cunningham
The Francis Crick institute, London NW1 1AT, UK.
Irene
I
Tumwine
The Francis Crick institute, London NW1 1AT, UK.
Garikai
G
Kushinga
The Francis Crick institute, London NW1 1AT, UK.
Sarah
S
McLaughlin
MRC National Institute for Medical Research, London NW7 1AA, UK.
Philip
P
Spence
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Ulrike
U
Böhme
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Mandy
M
Sanders
Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United States of America.
Solomon
S
Conteh
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Ellen
E
Bushell
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Tom
T
Metcalf
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Oliver
O
Billker
Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United States of America.
Patrick E
PE
Duffy
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.|Weatherall Institute of Molecular Medicine, Oxford OX3 9DS, UK.
Chris
C
Newbold
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Matthew
M
Berriman
The Francis Crick institute, London NW1 1AT, UK.
Jean
J
Langhorne
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008288:Malaria / Q000276:immunology / Q000469:parasitology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology; D051379:Mice; D010961:Plasmodium / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity*; D010963:Plasmodium falciparum / Q000235:genetics / Q000472:pathogenicity; D016790:Plasmodium knowlesi / Q000235:genetics / Q000472:pathogenicity; D037521:Virulence Factors / Q000235:genetics*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D037521:Virulence Factors