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)
Cerebral malaria (CM), mainly caused by
Plasmodium falciparum
(
P. f
.), is one of the most lethal complications of severe
malaria
. As immunopathology mediated by brain-infiltrating CD8
+
T cells is the major pathogenesis of CM, there is no safe and efficient treatment clinically focused on CD8
+
T cells. New methods are needed to protect the host from injury. As evidence has shown that programmed death-1 (PD-1) is one of the most efficient immunomodulatory molecules, we constructed two soluble fusion proteins, PDL1-IgG1Fc and
PDL2
-IgG1Fc, to enhance PD-1/PDL signaling pathways in innate and adaptive immune cells, including macrophages and CD8
+
T cells. Firstly, we confirmed that PD-1 signal pathway deficiency led to higher levels of CD8
+
T cell proliferation and shorter survival time in PD-1-deficient (
Pdcd1
-/-
) mice than WT mice. Secondly, PDL1-IgG1Fc-treated mice exhibited a more prolonged survival time than control groups. Moreover, PDL1-IgG1Fc was observed to ameliorate blood-brain barrier (BBB) disruption by limiting the over-reactive CD8
+
T cell cytotoxicity during experimental cerebral
malaria
(ECM). Further studies found thatPDL1-IgG1Fc-treated macrophages showed significant suppression in macrophage M1 polarization and their antigen presentation capability to CD8
+
T cells. In conclusion, our results demonstrated that the administration of PDL1-IgG1Fc in the early stage before ECM onset has an obvious effect on the maintenance of immune microenvironment homeostasis in the brain and is deemed a promising candidate for protection against CM in the future.
...
PMID:PDL1 Fusion Protein Protects Against Experimental Cerebral Malaria via Repressing Over-Reactive CD8
+
T Cell Responses. 3069 1
