Human natural killer cells control Plasmodium falciparum infection by eliminating infected red blood cells
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 s...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2014
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| Online Access: | http://hdl.handle.net/1721.1/89110 https://orcid.org/0000-0002-5687-6154 |
| _version_ | 1826190769641226240 |
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| author | Chen, Qingfeng Amaladoss, Anburaj Ye, Weijian Liu, Min Dummler, Sara Kong, Fang Wong, Lan Hiong Loo, Hooi Linn Loh, Eva Tan, Shu Qi Tan, Thiam Chye Chang, Kenneth T. E. Dao, Ming Suresh, Subra Preiser, Peter R. Chen, Jianzhu |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Chen, Qingfeng Amaladoss, Anburaj Ye, Weijian Liu, Min Dummler, Sara Kong, Fang Wong, Lan Hiong Loo, Hooi Linn Loh, Eva Tan, Shu Qi Tan, Thiam Chye Chang, Kenneth T. E. Dao, Ming Suresh, Subra Preiser, Peter R. Chen, Jianzhu |
| author_sort | Chen, Qingfeng |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:45:25Z |
| format | Article |
| id | mit-1721.1/89110 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:45:25Z |
| publishDate | 2014 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/891102022-09-23T14:18:51Z Human natural killer cells control Plasmodium falciparum infection by eliminating infected red blood cells Chen, Qingfeng Amaladoss, Anburaj Ye, Weijian Liu, Min Dummler, Sara Kong, Fang Wong, Lan Hiong Loo, Hooi Linn Loh, Eva Tan, Shu Qi Tan, Thiam Chye Chang, Kenneth T. E. Dao, Ming Suresh, Subra Preiser, Peter R. Chen, Jianzhu 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 Dao, Ming Chen, Jianzhu 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. Singapore-MIT Alliance for Research and Technology (Interdisciplinary Research Group in Infectious Disease Research Program) 2014-08-29T14:31:13Z 2014-08-29T14:31:13Z 2014-01 2013-10 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/89110 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. https://orcid.org/0000-0002-5687-6154 en_US http://dx.doi.org/10.1073/pnas.1323318111 Proceedings of the National Academy of Sciences 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. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Chen, Qingfeng Amaladoss, Anburaj Ye, Weijian Liu, Min Dummler, Sara Kong, Fang Wong, Lan Hiong Loo, Hooi Linn Loh, Eva Tan, Shu Qi Tan, Thiam Chye Chang, Kenneth T. E. Dao, Ming Suresh, Subra Preiser, Peter R. Chen, Jianzhu Human natural killer cells control Plasmodium falciparum infection by eliminating infected red blood cells |
| title | Human natural killer cells control Plasmodium falciparum infection by eliminating infected red blood cells |
| title_full | Human natural killer cells control Plasmodium falciparum infection by eliminating infected red blood cells |
| title_fullStr | Human natural killer cells control Plasmodium falciparum infection by eliminating infected red blood cells |
| title_full_unstemmed | Human natural killer cells control Plasmodium falciparum infection by eliminating infected red blood cells |
| title_short | Human natural killer cells control Plasmodium falciparum infection by eliminating infected red blood cells |
| title_sort | human natural killer cells control plasmodium falciparum infection by eliminating infected red blood cells |
| url | http://hdl.handle.net/1721.1/89110 https://orcid.org/0000-0002-5687-6154 |
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