Please use this identifier to cite or link to this item: https://doi.org/10.1073/pnas.1323318111
Title: Human natural killer cells control Plasmodium falciparum infection by eliminating infected red blood cells
Authors: Chen, Q.
Amaladoss, A.
Ye, W.
Liu, M.
Dummler, S.
Kong, F.
Wong, L.H.
Loo, H.L.
Loh, E.
Tan, S.Q.
Tan, T.C. 
Chang, K.T.E.
Dao, M.
Suresh, S.
Preiser, P.R.
Chen, J.
Keywords: Humanized mouse model
LFA-1
Malaria infection
NK killing
Issue Date: 28-Jan-2014
Citation: Chen, Q., Amaladoss, A., Ye, W., Liu, M., Dummler, S., Kong, F., Wong, L.H., Loo, H.L., Loh, E., Tan, S.Q., Tan, T.C., Chang, K.T.E., Dao, M., Suresh, S., Preiser, P.R., Chen, J. (2014-01-28). Human natural killer cells control Plasmodium falciparum infection by eliminating infected red blood cells. Proceedings of the National Academy of Sciences of the United States of America 111 (4) : 1479-1484. ScholarBank@NUS Repository. https://doi.org/10.1073/pnas.1323318111
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.
Source Title: Proceedings of the National Academy of Sciences of the United States of America
URI: http://scholarbank.nus.edu.sg/handle/10635/124635
ISSN: 00278424
DOI: 10.1073/pnas.1323318111
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