Flandin, Jean-Frédéric; Chano, Frédéric et Descoteaux, Albert 
ORCID: https://orcid.org/0000-0002-0633-5309
(2006).
RNA interference reveals a role for TLR2 and TLR3 in the recognition of Leishmania donovani promastigotes by interferon-gamma-primed macrophages
European Journal of Immunology
, vol. 36
, nº 2.
pp. 411-420.
DOI: 10.1002/eji.200535079.
Résumé
Leishmania donovani promastigotes evade the induction of a proinflammatory response during their invasion of naive macrophages. However,,their entry into IFN-gamma-primed macrophages is accompanied by the secretion of nitric oxide (NO) and proinflammatory cytokines. In the present study, we addressed the hypothesis that priming with IFN-gamma induces the expression of a receptor that enables mouse macrophages to recognize L. donovani promastigotes. We observed that in IFN-gamma-primed macrophages, L. donovani promastigotes stimulated Interleukin-1 receptor-associated kinase-1 (IRAK-1) activity. We next showed that Toll-like receptor (TLR) 3 is barely detectable in naive macrophages but is expressed in IFN-gamma-treated macrophages. Silencing of TLR3, TLR2, IRAK-1 and myeloid differentiation factor 88 (MyD88) expression by RNA interference revealed that both TLR are involved in the secretion of NO and TNF-alpha induced by L. donovani promastigotes. Using L. donovani mutants, we showed that TLR2-mediated responses are dependent on Gal beta 1,4Man alpha-PO4-containing phosphoglycans, whereas TLR3-mediated responses are independent of these glycoconjugates. Furthermore, our data indicate a participation of TLR2 and TLR3 in the phagocytosis of L. donovani promastigotes and a role for TLR3 in the leishmanicidal activity of the IFN-gamma-primed macrophages. Collectively, our data are consistent with a model where recognition of L. donovani promastigotes depends on the macrophage activation status and requires the expression of TLR3.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | Innate immunity; Leishmania; Macrophages; Phagocytosis; Toll-like receptors |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 01 nov. 2024 14:58 |
| Dernière modification: | 01 nov. 2024 14:58 |
| URI: | https://espace.inrs.ca/id/eprint/14659 |
Gestion Actions (Identification requise)
 |
Modifier la notice |