Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0024530 (
malaria
)
44,886
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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 10
6
P. 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
.
...
PMID:Protective Vaccination Reshapes Hepatic Response to Blood-Stage Malaria of Genes Preferentially Expressed by NK Cells. 3320 67
