The parasite intraerythrocytic cycle and human circadian cycle are coupled during malaria infection
Abstract
During infections with the malaria parasites Plasmodium vivax , patients exhibit rhythmic fevers every 48 h. These fever cycles correspond with the time the parasites take to traverse the intraerythrocytic cycle (IEC). In other Plasmodium species that infect either humans or mice, the IEC is likely guided by a parasite-intrinsic clock [Rijo-Ferreira et al. , Science 368 , 746–753 (2020); Smith et al ., Science 368 , 754–759 (2020)], suggesting that intrinsic clock mechanisms may be a fundamental feature of malaria parasites. Moreover, because Plasmodium cycle times are multiples of 24 h, the IECs may be coordinated with the host circadian clock(s). Such coordination could explain the synchronization of the parasite population in the host and enable alignment of IEC and circadian cycle phases. We utilized an ex vivo culture of whole blood from patients infected with P. vivax to examine the dynamics of the host circadian transcriptome and the parasite IEC transcriptome. Transcriptome dynamics revealed that the phases of the host circadian cycle and the parasite IEC are correlated across multiple patients, showing that the cycles are phase coupled. In mouse model systems, host–parasite cycle coupling appears to provide a selective advantage for the parasite. Thus, understanding how host and parasite cycles are coupled in humans could enable antimalarial therapies that disrupt this coupling.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 06, 2023
- Source ID
- 10.1073/pnas.2216522120
Entities
People
- Adam R Leman
- Chadin Thongpiam
- Chatchadaporn Thamnurak
- Christina M Kelliher
- Chun-yi Cho
- Francis C Motta
- Ilin Chuang
- John Harer
- Kevin Mcgoff
- Krisada Jongsakul
- Lauren M Smith
- Mariusz Wojnarski
- Michael S. Ortiz
- Michele D Spring
- Montri Arsanok
- Nichaphat Uthaimongkol
- Nicolas Devos
- Nonlawat Boonyalai
- Pattaraporn Vanchayangkul
- Philip L. Smith
- Robert C Moseley
- Sophia A. Campione
- Steve Haase
- Suwanna Chaorattanakawee
- Worachet Kuntawunginn
Organizations
- Armed Forces Research Institute of Medical Sciences
- Duke University
- Florida Atlantic University
- Geisel School of Medicine
- Mahidol University
- National Institutes of Health
- National Science Foundation
- University of California
- University of North Carolina
- Walter Reed Army Institute of Research
- Walter Reed National Military Medical Center