Innate Lymphocytes and Malaria – Players or Spectators?

Ng, Susanna S.; Engwerda, Christian

doi:10.1016/j.pt.2018.11.012

Cited by 1 publication

(6 citation statements)

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“…LrNK cells have been described to express the surface ligand TRAIL encoded by Tnfsf10 and cNK cells the transcription factor eomesodermin encoded by Eomes, while the transcription factor T-bet encoded by Tbx21 is expressed in both cNK cells and lrNK cells [12,33]. Figure 1 shows that Tnfsf10 reveals a high constitutive expression, which is in the range of that of Itga1.…”

Section: Vaccination Reshapes the Response To Blood-stage Malaria Of Genes Expressed By Lrnk And Cnk Cells In The Livermentioning

confidence: 99%

“…In particular, Kupffer cells with their erythrophagocytic capacity are currently regarded as mainly responsible for removal of Plasmodium-infected erythrocytes in the liver [7][8][9][10]. Moreover, there is increasing information, though controversially debated, that natural killer (NK) cells in the liver may also play a critical role in the elimination of Plasmodium-infected erythrocytes [11,12]. Indeed, their innate cytotoxic activity makes NK cells an important player in the first-line defense against Plasmodium-infected erythrocytes long before activation and development of adaptive immune mechanisms [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, there is increasing information, though controversially debated, that natural killer (NK) cells in the liver may also play a critical role in the elimination of Plasmodium-infected erythrocytes [11,12]. Indeed, their innate cytotoxic activity makes NK cells an important player in the first-line defense against Plasmodium-infected erythrocytes long before activation and development of adaptive immune mechanisms [12][13][14]. Nevertheless, NK cells may be even capable of shaping subsequent adaptive immune mechanisms and also possess memory-like adaptive immune features [13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

“…NK cells encompass heterogeneous cell populations and are currently considered as a special subset of group 1 innate lymphoid cells (ILC1s) [11,12,18]. Their common function is to kill diseased cells such as virus-infected, tumor, and stressed cells by releasing perforin and granzymes from their cytoplasmic vesicles via exocytosis, which induce apoptosis of the targeted cells.…”

Section: Introductionmentioning

confidence: 99%

“…The lrNK cells are presumably derived from liver-resident progenitor cells and are therefore thought to represent a distinct lineage of NK cells, which are different from circulating conventional NK (cNK) cells. The cNK cells are characterized by surface expression of CD49b and the transcription factors eomesodermin (Eomes) and T-bet, while the lrNK cells express only T-bet, TRAIL, and CD49a (for reviews see [12] and [33]). However, it has not been investigated yet whether the relative proportions of lrNK and cNK cells in the liver are affected by vaccination and/or blood-stage malaria, respectively.…”

Section: Introductionmentioning

confidence: 99%

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Protective Vaccination Reshapes Hepatic Response to Blood-Stage Malaria of Genes Preferentially Expressed by NK Cells

et al. 2020

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The role of natural killer (NK) cells in the liver as first-line post infectionem (p.i.) effectors against blood-stage malaria and their responsiveness to protective vaccination is poorly understood. Here, we investigate the effect of vaccination on NK cell-associated genes induced in the liver by blood-stage malaria of Plasmodium chabaudi. Female Balb/c mice were vaccinated at weeks 3 and 1 before being infected with 106P. chabaudi-parasitized erythrocytes. Genes preferentially expressed by NK cells were investigated in livers of vaccination-protected and non-protected mice on days 0, 1, 4, 8, and 11 p.i. using microarrays, qRT-PCR, and chromosome landscape analysis. Blood-stage malaria induces expression of specific genes in the liver at different phases of infection, i.e., Itga1 in expanding liver-resident NK (lrNK) cells, Itga2 in immigrating conventional NK (cNK) cells; Eomes and Tbx21 encoding transcription factors; Ncr1, Tnfsf10, Prf1, Gzma, Gzmb, Gzmc, Gzmm, and Gzmk encoding cytolytic effectors; natural killer gene complex (NKC)-localized genes encoding the NK cell receptors KLRG1, KLRK1, KLRAs1, 2, 5, 7, KLRD1, KLRC1, KLRC3, as well as the three receptors KLRB1A, KLRB1C, KLRB1F and their potential ligands CLEC2D and CLEC2I. Vaccination enhances this malaria-induced expression of genes, but impairs Gzmm expression, accelerates decline of Tnfsf10 and Clec2d expression, whereas it accelerates increased expression of Clec2i, taking a very similar time course as that of genes encoding plasma membrane proteins of erythroblasts, whose malaria-induced extramedullary generation in the liver is known to be accelerated by vaccination. Collectively, vaccination reshapes the response of the liver NK cell compartment to blood-stage malaria. Particularly, the malaria-induced expansion of lrNK cells peaking on day 4 p.i. is highly significantly (p < 0.0001) reduced by enhanced immigration of peripheral cNK cells, and KLRB1F:CLEC2I interactions between NK cells and erythroid cells facilitate extramedullary erythroblastosis in the liver, thus critically contributing to vaccination-induced survival of otherwise lethal blood-stage malaria of P. chabaudi.

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Section: Vaccination Reshapes the Response To Blood-stage Malaria Of Genes Expressed By Lrnk And Cnk Cells In The Livermentioning

confidence: 99%