Plasmodium berghei TatD-like DNase hijacks host innate immunity by inhibiting the TLR9-NF-κB pathway.
Int Immunopharmacol
; 140: 112843, 2024 Oct 25.
Article
de En
| MEDLINE
| ID: mdl-39098224
ABSTRACT
Neutrophils and macrophages confine pathogens by entrapping them in extracellular traps (ETs) through activating TLR9 function. However, plasmodial parasites secreted TatD-like DNases (TatD) to counteract ETs-mediated immune clearance. We found that TLR9 mutant mice increased susceptibility to rodent malaria, suggesting TLR9 is a key protein for host defense. We found that the proportion of neutrophils and macrophages in response to plasmodial parasite infection in the TLR9 mutant mice was significantly reduced compared to that of the WT mice. Importantly, PbTatD can directly bind to the surface TLR9 (sTLR9) on macrophages, which blocking the phosphorylation of mitogen-activated protein kinase and nuclear factor-κB, negatively regulated the signaling of ETs formation by both macrophages and neutrophils. Such, P. berghei TatD is a parasite virulence factor that can inhibit the proliferation of macrophages and neutrophils through directly binding to TLR9 receptors on the cell surface, thereby blocking the activation of the downstream MyD88-NF-kB pathways.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Plasmodium berghei
/
Transduction du signal
/
Désoxyribonucléases
/
Immunité innée
/
Macrophages
/
Paludisme
/
Granulocytes neutrophiles
Limites:
Animals
/
Humans
Langue:
En
Journal:
Int Immunopharmacol
/
Int. immunopharmacol
/
International immunopharmacology
Sujet du journal:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Année:
2024
Type de document:
Article
Pays de publication:
Pays-Bas