Title :

Role of astrocyte senescence regulated by the non- canonical autophagy in the neuroinflammation associated to cerebral malaria.

Author(s) :

Hellani, Fatima [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Leleu, Inès [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Saidi, Nasreddine [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Martin, Nathalie [Auteur]
Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277
Lecoeur, Cecile [Auteur]
Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017
Werkmeister, Elisabeth [Auteur]
Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS]
Koffi, D. [Auteur]
Trottein, Francois [Auteur]
Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017
Yapo-Etté, H. [Auteur]
Das, B. [Auteur]
Abbadie, Corinne [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Pied, Sylviane [Auteur]
Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Journal title :

Brain, Behavior, and Immunity

Abbreviated title :

Brain Behav Immun

Volume number :

117

Pages :

p. 20-35

Publication date :

2024-03

ISSN :

1090-2139

English keyword(s) :

Astrocyte
Cellular senescence
P21
Cerebral malaria
Inflammation
Senolytic drugs

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Background Cerebral malaria (CM) is a fatal neuroinflammatory syndrome caused (in humans) by the protozoa Plasmodium (P.) falciparum. Glial cell activation is one of the mechanisms that contributes to neuroinflammation ...
Show more >Background Cerebral malaria (CM) is a fatal neuroinflammatory syndrome caused (in humans) by the protozoa Plasmodium (P.) falciparum. Glial cell activation is one of the mechanisms that contributes to neuroinflammation in CM. Result By studying a mouse model of CM (caused by P. berghei ANKA), we describe that the induction of autophagy promoted p21-dependent senescence in astrocytes and that CXCL-10 was part of the senescence-associated secretory phenotype. Furthermore, p21 expression was observed in post-mortem brain and peripheral blood samples from patients with CM. Lastly, we found that the depletion of senescent astrocytes with senolytic drugs abrogated inflammation and protected mice from CM. Conclusion Our data provide evidence for a novel mechanism through which astrocytes could be involved in the neuropathophysiology of CM. p21 gene expression in blood cell and an elevated plasma CXCL-10 concentration could be valuable biomarkers of CM in humans. In the end, we believe senolytic drugs shall open up new avenues to develop newer treatment options.Show less >

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277
• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017
• Plateformes Lilloises en Biologie et Santé (PLBS) - UAR 2014 - US 41

Submission date :

2024-03-01T22:01:28Z
2024-03-04T18:28:30Z
2024-03-04T18:35:37Z