Rapid loss of group 1 innate lymphoid cells during blood stage Plasmodium infection

Thumbnail Image
File version

Version of Record (VoR)

Ng, Susanna S
Souza-Fonseca-Guimaraes, Fernando
Rivera, Fabian de Labastida
Amante, Fiona H
Kumar, Rajiv
Gao, Yulong
Sheel, Meru
Beattie, Lynette
de Oca, Marcela Montes
Guillerey, Camille
Edwards, Chelsea L
Faleiro, Rebecca J
Frame, Teija
Bunn, Patrick T
Vivier, Eric
Godfrey, Dale I
Pellicci, Daniel G
Lopez, J Alejandro
Andrews, Katherine T
Huntington, Nicholas D
Smyth, Mark J
McCarthy, James
Engwerda, Christian R
Primary Supervisor
Other Supervisors
File type(s)

Objectives 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 during Plasmodium infection.

Methods We quantified group 1 ILCs in peripheral blood collected from subjects infected with with Plasmodium falciparum 3D7 as part of a controlled human malaria infection study, and in the liver and spleens of PcAS-infected mice. We used genetically-modified mouse models, as well as cell-depletion methods in mice to characterise the role of group 1 ILCs during PcAS infection.

Results 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 in P. chabaudi chabaudi AS (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 during PcAS infection in mice.

Discussion Our results are consistent with a previous study indicating a limited role for natural killer (NK) cells during Plasmodium chabaudi infection 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.

Conclusion 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.

Journal Title

Clinical & Translational Immunology

Conference Title
Book Title




Thesis Type
Degree Program
Publisher link
Patent number
Grant identifier(s)
Rights Statement
Rights Statement

© 2018 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australasian Society for Immunology Inc.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Item Access Status
Access the data
Related item(s)


Cellular immunology

Pharmacology and pharmaceutical sciences

Persistent link to this record