Mapping immune variation and var gene switching in naïve hosts infected with Plasmodium falciparum
Kathryn H. Milne,Alasdair Ivens,Adam J. Reid,Magda E. Lotkowska,Áine O'Toole,Geetha Sankaranarayanan,Diana Munoz Sandoval,Diana Munoz Sandoval,Wiebke Nahrendorf,Clément Regnault,Nick J. Edwards,Sarah E. Silk,Ruth O. Payne,Angela M. Minassian,N Venkatraman,Mandy Sanders,Adrian V. S. Hill,Michael P. Barrett,Matthew Berriman,Simon J. Draper,J. Alexandra Rowe,Philip J Spence +21 more
TLDR
In this paper, the authors explored the interaction between inflammation and parasite variant surface antigen (VSA) expression, asking whether this relationship underpins the variation observed in controlled human malaria infection (CHMI).Abstract:
Falciparum malaria is clinically heterogeneous and the relative contribution of parasite and host in shaping disease severity remains unclear. We explored the interaction between inflammation and parasite variant surface antigen (VSA) expression, asking whether this relationship underpins the variation observed in controlled human malaria infection (CHMI). We uncovered marked heterogeneity in the host response to blood challenge; some volunteers remained quiescent, others triggered interferon-stimulated inflammation and some showed transcriptional evidence of myeloid cell suppression. Significantly, only inflammatory volunteers experienced hallmark symptoms of malaria. When we tracked temporal changes in parasite VSA expression to ask whether variants associated with severe disease rapidly expand in naive hosts, we found no transcriptional evidence to support this hypothesis. These data indicate that parasite variants that dominate severe malaria do not have an intrinsic growth or survival advantage; instead, they presumably rely upon infection-induced changes in their within-host environment for selection.read more
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Expression Patterns of Plasmodium falciparum Clonally Variant Genes at the Onset of a Blood Infection in Malaria-Naive Humans.
Anastasia K. Pickford,Lucas Michel-Todó,Florian Dupuy,Alfredo Mayor,Pedro L. Alonso,Catherine Lavazec,Alfred Cortés +6 more
TL;DR: In this paper, the authors provided a detailed characterization of the complete P. falciparum transcriptome across the full intraerythrocytic development cycle (IDC) at the onset of a blood infection in malaria-naive human volunteers.
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Dramatic transcriptomic differences in Macaca mulatta and Macaca fascicularis with Plasmodium knowlesi infections.
Anuj Gupta,Mark P. Styczynski,Mary R. Galinski,Mary R. Galinski,Eberhard O. Voit,Luis L. Fonseca,Luis L. Fonseca +6 more
TL;DR: In this article, the authors compared P. knowlesi sporozoite-initiated infections in Macaca mulatta and Macaca fascicularis using whole blood RNA-sequencing and transcriptomic analysis.
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Controlled human malaria infections by mosquito bites induce more severe clinical symptoms than asexual blood-stage challenge infections
Manon Alkema,Xi Zen Yap,Gerdie M. de Jong,Isaie J. Reuling,Quirijn de Mast,Reinout van Crevel,Christian F. Ockenhouse,Katharine A. Collins,Teun Bousema,Matthew B. B. McCall,Robert W. Sauerwein +10 more
TL;DR: In this article , the authors compared clinical inflammation in healthy malaria-naïve volunteers infected by either Plasmodium falciparum (Pf)infected mosquito bites (MB, n=12) or intravenous administration of Pf-infected red blood cells (BS), and concluded that Pfinfections by MB induce stronger signs and symptoms of inflammation compared to CHMI by BS infection.
Journal ArticleDOI
Systems biology of malaria explored with nonhuman primates
TL;DR: A review of NHP-NHP infection model systems can be found in this article , with emphasis on modern systems biological approaches to studying longitudinal infections, pathogenesis, immunity, and vaccines.
Journal ArticleDOI
Systems biology of malaria explored with nonhuman primates
TL;DR: A review of NHP-NHP infection model systems can be found in this article , with emphasis on modern systems biological approaches to studying longitudinal infections, pathogenesis, immunity, and vaccines.
References
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