Differential Spleen Remodeling Associated with Different Levels of Parasite Virulence Controls Disease Outcome in Malaria Parasite Infections.
Infections by malaria parasites can lead to very different clinical outcomes, ranging from mild symptoms to death. Differences in the ability of the spleen to deal with the infected red blood cells (iRBCs) are linked to differences in virulence. Using virulent and avirulent strains of the rodent malaria parasite Plasmodium yoelii, we investigated how parasite virulence modulates overall spleen function. Following parasite invasion, a difference in parasite virulence was observed in association with different levels of spleen morphology and iRBC rigidity, both of which contributed to enhanced parasite clearance. Moreover, iRBC rigidity as modulated by the spleen was demonstrated to correlate with disease outcome and thus can be used as a robust indicator of virulence. The data indicate that alterations in the biomechanical properties of iRBCs are the result of the complex interaction between host and parasite. Furthermore, we confirmed that early spleen responses are a key factor in directing the clinical outcome of an infection. IMPORTANCE The spleen and its response to parasite infection are important in eliminating parasites in malaria. By comparing P. yoelii parasite lines with different disease outcomes in mice that had either intact spleens or had had their spleens removed, we showed that upon parasite infection, the spleen exhibits dramatic changes that can affect parasite clearance. The spleen itself directly impacts RBC deformability independently of parasite genetics. The data indicated that the changes in the biomechanical properties of malaria parasite-infected RBCs are the result of the complex interaction between host and parasite, and RBC deformability itself can serve as a novel predictor of clinical outcome. The results also suggest that early responses in the spleen are a key factor directing the clinical outcome of an infection.
School of Biological Science, Nanyang Technological University, Singapore.
Ximei
X
Huang
Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, Singapore.
Sha
S
Huang
Center for BioImaging Sciences, National University of Singapore, Singapore; Department of Biological Sciences, National University of Singapore, Singapore.
Lai Chun
LC
Ong
Clinical Imaging Research Center, National University of Singapore, Singapore.
Jason Chu-Shern
JC
Lim
School of Biological Science, Nanyang Technological University, Singapore.
Rebecca Joan Mary
RJ
Hurst
School of Biological Science, Nanyang Technological University, Singapore.
Annals Tatenda
AT
Mushunje
Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, Singapore; Center for BioImaging Sciences, National University of Singapore, Singapore; Department of Biological Sciences, National University of Singapore, Singapore; MechanoBiology Institute-Singapore, National University of Singapore, Singapore.
Paul Thomas
PT
Matsudaira
Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, Singapore.
Jongyoon
J
Han
School of Biological Science, Nanyang Technological University, Singapore.
Peter Rainer
PR
Preiser
innate immunity; malaria; marker; red blood cell rigidity; virulence