Differential Spleen Remodeling Associated with Different Levels of Parasite Virulence Controls Disease Outcome in Malaria Parasite Infections

Author:

Huang Ximei1,Huang Sha23,Ong Lai Chun45,Lim Jason Chu-Shern6,Hurst Rebecca Joan Mary1,Mushunje Annals Tatenda1,Matsudaira Paul Thomas3457,Han Jongyoon283,Preiser Peter Rainer1

Affiliation:

1. School of Biological Science, Nanyang Technological University, Singapore

2. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

3. Biosystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, Singapore

4. Center for BioImaging Sciences, National University of Singapore, Singapore

5. Department of Biological Sciences, National University of Singapore, Singapore

6. Clinical Imaging Research Center, National University of Singapore, Singapore

7. MechanoBiology Institute-Singapore, National University of Singapore, Singapore

8. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

Abstract

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.

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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