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)
A large proportion of the death toll associated with
malaria
is a consequence of
malaria
infection during pregnancy, causing up to 200,000 infant deaths annually. We previously published the first extensive genetic association study of placental
malaria
infection, and here we extend this analysis considerably, investigating genetic variation in over 9,000 SNPs in more than 1,000 genes involved in immunity and inflammation for their involvement in susceptibility to placental
malaria
infection. We applied a new approach incorporating results from both single gene analysis as well as gene-gene interactions on a protein-protein interaction network. We found suggestive associations of variants in the gene
KLRK1
in the single gene analysis, as well as evidence for associations of multiple members of the IL-7/IL-7R signalling cascade in the combined analysis. To our knowledge, this is the first large-scale genetic study on placental
malaria
infection to date, opening the door for follow-up studies trying to elucidate the genetic basis of this neglected form of
malaria
.
...
PMID:A targeted association study of immunity genes and networks suggests novel associations with placental malaria infection. 2194 27
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
