Abstract
ObjectivesInnate 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.MethodsWe 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 Pc AS‐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 Pc AS infection.ResultsIn 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 (Pc AS)‐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 Pc AS infection in mice.DiscussionOur 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.ConclusionOur 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.
Highlights
Innate lymphoid cells (ILCs) resemble T helper (Th) cells in terms of their characteristic transcription factors and functions.[1]
Given that group 1 ILCs function like T helper 1 (Th1) cells, and little is known about their roles during Plasmodium infection, we examined these cells, as well as the more well-studied innate-like T cells (including cd T cells,[28] invariant natural killer T cells[30,31] and mucosal-associated invariant T (MAIT) cells32) in volunteers infected with Plasmodium falciparum (Pf) in controlled human malaria infection (CHMI) studies
We report that conventional natural killer (cNK) cells and ILC1s had a limited role in controlling peripheral blood parasitaemia in mice infected with P. chabaudi chabaudi AS (PcAS)
Summary
Innate lymphoid cells (ILCs) resemble T helper (Th) cells in terms of their characteristic transcription factors and functions.[1] Groups 1, 2 and 3 ILCs make up the ILC repertoire, and these groups are similar to Th1, Th2 and Th17 cells, respectively. Group 1 ILCs consist of conventional natural killer (cNK) cells and ILC1s.1,6. These cell subsets share common developmental requirements for the transcription factor T-bet and their ability to produce the pro-inflammatory cytokine IFNc.[6] the relationship between these cells is still widely debated. These different tissue-resident subsets have unique cell surface phenotypes and functions.[4,9,13]
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