Human natural killer cells control Plasmodium falciparum infection by eliminating infected red blood cells
Name
Chen-2014-Human natural killer.pdf
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Author(s)
Chen, Qingfeng
Amaladoss, Anburaj
Ye, Weijian
Liu, Min
Dummler, Sara
Kong, Fang
Wong, Lan Hiong
Loo, Hooi Linn
Loh, Eva
Tan, Shu Qi
Date Issued
January 2014
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Chen, Q., A. Amaladoss, W. Ye, M. Liu, S. Dummler, F. Kong, L. H. Wong, et al. “Human Natural Killer Cells Control Plasmodium Falciparum Infection by Eliminating Infected Red Blood Cells.” Proceedings of the National Academy of Sciences 111, no. 4 (January 28, 2014): 1479–1484.
Version
Final published version
Abstract
Immunodeficient mouse–human chimeras provide a powerful approach to study host-specific pathogens, such as Plasmodium falciparum that causes human malaria. Supplementation of immunodeficient mice with human RBCs supports infection by human Plasmodium parasites, but these mice lack the human immune system. By combining human RBC supplementation and humanized mice that are optimized for human immune cell reconstitution, we have developed RBC-supplemented, immune cell-optimized humanized (RICH) mice that support multiple cycles of P. falciparum infection. Depletion of human natural killer (NK) cells, but not macrophages, in RICH mice results in a significant increase in parasitemia. Further studies in vitro show that NK cells preferentially interact with infected RBCs (iRBCs), resulting in the activation of NK cells and the elimination of iRBCs in a contact-dependent manner. We show that the adhesion molecule lymphocyte-associated antigen 1 is required for NK cell interaction with and elimination of iRBCs. Development of RICH mice and validation of P. falciparum infection should facilitate the dissection of human immune responses to malaria parasite infection and the evaluation of therapeutics and vaccines.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1323318111
