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)
Natural Killer (NK) cells play an essential role in antiviral and anti-tumoral immune responses. In peripheral blood, NK cells are commonly classified into two major subsets: CD56
bright
CD16
neg
and CD56
dim
CD16
pos
despite the characterization of a CD56
neg
CD16
pos
subset 25 years ago. Since then, several studies have described the prevalence of an CD56
neg
CD16
pos
NK cell subset in viral non-controllers as the basis for their NK cell dysfunction. However, the mechanistic basis for their cytotoxic impairment is unclear. Recently, using a strict flow cytometry gating strategy to exclude monocytes, we reported an accumulation of CD56
neg
CD16
pos
NK cells in
Plasmodium falciparum
malaria
-exposed children and pediatric cancer patients diagnosed with endemic Burkitt lymphoma (eBL). Here, we use live-sorted cells, histological staining, bulk RNA-sequencing and flow cytometry to confirm that this CD56
neg
CD16
pos
NK cell subset has the same morphological features as the other NK cell subsets and a similar transcriptional profile compared to CD56
dim
CD16
pos
NK cells with only 120 genes differentially expressed (fold change of 1.5,
p
< 0.01 and FDR<0.05) out of 9235 transcripts. CD56
neg
CD16
pos
NK cells have a distinct profile with significantly higher expression of
MPEG1
(perforin 2),
FCGR3B
(CD16b),
FCGR2A
, and
FCGR2B
(CD32A and B) as well as
CD6, CD84, HLA-DR, LILRB1/2
, and
PDCD1
(PD-1), whereas Interleukin 18 (IL18) receptor genes (
IL18RAP
and
IL18R1
), cytotoxic genes such as
KLRF1
(NKp80) and
NCR1
(NKp46), and inhibitory
HAVCR2
(TIM-3) are significantly down-regulated compared to CD56
dim
CD16
pos
NK cells. Together, these data confirm that CD56
neg
CD16
pos
cells are legitimate NK cells, yet their transcriptional and protein expression profiles suggest their cytotoxic potential is mediated by pathways reliant on antibodies such as antibody-dependent cell cytotoxicity (ADCC), antibody-dependent respiratory burst (ADRB), and enhanced by complement receptor 3 (CR3) and FAS/FASL interaction. Our findings support the premise that chronic diseases induce NK cell modifications that circumvent proinflammatory mediators involved in direct cytotoxicity. Therefore, individuals with such altered NK cell profiles may respond differently to NK-mediated immunotherapies, infections or vaccines depending on which cytotoxic mechanisms are being engaged.
...
PMID:A New Hope for CD56
neg
CD16
pos
NK Cells as Unconventional Cytotoxic Mediators: An Adaptation to Chronic Diseases. 3237 55
