Title |
Rapid loss of group 1 innate lymphoid cells during blood stage Plasmodium infection
|
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Published in |
Clinical and Translational Immunology, January 2018
|
DOI | 10.1002/cti2.1003 |
Pubmed ID | |
Authors |
Susanna S Ng, Fernando Souza‐Fonseca‐Guimaraes, Fabian de Labastida Rivera, Fiona H Amante, Rajiv Kumar, Yulong Gao, Meru Sheel, Lynette Beattie, Marcela Montes de Oca, Camille Guillerey, Chelsea L Edwards, Rebecca J Faleiro, Teija Frame, Patrick T Bunn, Eric Vivier, Dale I Godfrey, Daniel G Pellicci, J Alejandro Lopez, Katherine T Andrews, Nicholas D Huntington, Mark J Smyth, James McCarthy, Christian R Engwerda |
Abstract |
Innate lymphoid cells (ILCs) share many characteristics with CD4+T cells, and group 1 ILCs share a requirement for T-bet and the ability to produce IFNγ with T helper 1 (Th1) cells. Given this similarity, and the importance of Th1 cells for protection against intracellular protozoan parasites, we aimed to characterise the role of group 1 ILCs duringPlasmodiuminfection. We quantified group 1 ILCs in peripheral blood collected from subjects infected with withPlasmodium falciparum3D7 as part of a controlled human malaria infection study, and in the liver and spleens ofPcAS-infected mice. We used genetically-modified mouse models, as well as cell-depletion methods in mice to characterise the role of group 1 ILCs duringPcAS infection. In a controlled human malaria infection study, we found that the frequencies of circulating ILC1s and NK cells decreased as infection progressed but recovered after volunteers were treated with antiparasitic drug. A similar observation was made for liver and splenic ILC1s inP. chabaudi chabaudiAS (PcAS)-infected mice. The decrease in mouse liver ILC1 frequencies was associated with increased apoptosis. We also identified a population of cells within the liver and spleen that expressed both ILC1 and NK cell markers, indicative of plasticity between these two cell lineages. Studies using genetic and cell-depletion approaches indicated that group 1 ILCs have a limited role in antiparasitic immunity duringPcAS infection in mice. Our results are consistent with a previous study indicating a limited role for natural killer (NK) cells duringPlasmodium chabaudiinfection in mice. Additionally, a recent study reported the redundancy of ILCs in humans with competent B and T cells. Nonetheless, our results do not rule out a role for group 1 ILCs in human malaria in endemic settings given that blood stage infection was initiated intravenously in our experimental models, and thus bypassed the liver stage of infection, which may influence the immune response during the blood stage. Our results show that ILC1s are lost early during mouse and human malaria, and this observation may help to explain the limited role for these cells in controlling blood stage infection. |
X Demographics
Geographical breakdown
Country | Count | As % |
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France | 1 | 25% |
Australia | 1 | 25% |
Unknown | 2 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 75% |
Scientists | 1 | 25% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 39 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 11 | 28% |
Researcher | 5 | 13% |
Student > Bachelor | 2 | 5% |
Student > Master | 2 | 5% |
Professor | 2 | 5% |
Other | 3 | 8% |
Unknown | 14 | 36% |
Readers by discipline | Count | As % |
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Immunology and Microbiology | 15 | 38% |
Medicine and Dentistry | 3 | 8% |
Biochemistry, Genetics and Molecular Biology | 1 | 3% |
Agricultural and Biological Sciences | 1 | 3% |
Nursing and Health Professions | 1 | 3% |
Other | 2 | 5% |
Unknown | 16 | 41% |