Toll like receptor 9 activation in Type 2 diabetes

Responsable de l’encadrement : Bénédicte Manoury

Tél : 0140615382  E-mail:,

Institut Nacker Enfants Malades

Résumé du Projet de Stage

Type 2 Diabetes (T2D) is an inflammatory disease which damages the pancreatic islets and leads to insufficient insulin production resulting in hyperglycemia. During metabolic dysfunction, a hallmark of T2D, experimental and clinical data have shown that an inflammatory response develops in the adipose tissue as well as in pancreatic islets, leading to the accumulation of macrophages secreting pro-inflammatory cytokines. However, what triggers this inflammation in adipose tissue and pancreatic islets is still unknown.

Toll like receptor 9 (TLR9) is an immune innate receptor highly expressed by macrophages and its activation leads to production of proinflammatory cytokines and inflammation.

In this project, we will investigate the role of TLR9 in T2D using mice lacking TLR9 or conditionally deficient for intracellular TLR9 signaling in macrophages (LysM-Cre crossed with floxed TLR9 mice).

 Dernières Publications en lien avec le projet :

– Tohme M,……, Manoury B. TLR7 trafficking and signaling in B cells is regulated by the MHC-II associated invariant chain. J Cell Science 2020 Mar 10;133(5):jcs236711. doi: 10.1242/jcs.236711.

– Maatouk L,……, Manoury B, Vyas S. TLR9 activation via microglial glucocorticoid receptors contributes to degeneration of midbrain dopamine neurons. Nat Commun 2018 Jun 22 ;9 (1)2450.

– Nunes-Hasler P,…., Manoury B, Demaurex N. STIM1 promotes migration, phagosomal maturation and antigen cross- presentation in dendritic cells. 2017 Nat Commun Nov 24;8(1):1852.

– Maschalidi S,……, Darasse-Jèze G, Manoury B. UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells. 2017 Nat Commun. Nov 21;8(1):1640.

– Babdor J,…., Manoury B* Saveanu L*. IRAP+ endosomes restrict TLR9 activation and signaling.  2017 Nat Immunol May;18(5):509-518. *Co-last and corresponding authors

– Orliaguet L …..Venteclef N, Alzaid F. Mechanisms of macrophages polarization in insulin signaling and sensitivity. Front Endocrinol 2020 19:11-62.

– Drareni K,…..Venteclef N. Adipocyte reprogramming by the transcriptional coregulator  GPS2 impacts beta cell insulin secretion. Cell Rep 2020 15;32(11):108141.

– Drareni K, ….Venteclef N. GPS2 deficiency triggers maladaptive white adipose tissue expansion in obesity via HIF1A activation. Cell Rep 2018 11;24(11):2957-2971.

– Dalmas E,…..Venteclef N. Irf5 deficiency in macrophages promotes beneficial adipose tissue expansion and insulin sensitivity during obesity. Nat Med 2015 21(6):610-8.

Ce projet s’inscrit dans la perspective d’une thèse

 Ecole Doctorale de rattachement :

D BioSPC 562


Intitulé de l’Unité : Institut Necker Enfants Malades

Nom du Responsable de l’Unité : Fabiola Terzi

Nom du Responsable de l’Équipe : Bénédicte Manoury

Adresse : 156-160 rue de sèvres