Loading...
Please wait, while we are loading the content...
Similar Documents
Dendritic Cell Differentiation State and Their Interaction with NKT Cells Determine Th1/Th2 Differentiation in the Murine Model ofLeishmania majorInfection
| Content Provider | Scilit |
|---|---|
| Author | Wiethe, Carsten Debus, Andrea Mohrs, Markus Steinkasserer, Alexander Lutz, Manfred Gessner, André |
| Copyright Year | 2008 |
| Description | Recent reports demonstrated that dendritic cells (DC) sense inflammatory and microbial signals differently, redefining their classical subdivision into an immature endocytic and a mature Ag-presenting differentiation stage. Although both signals induce DC maturation by up-regulating MHC class II and costimulatory molecules, only TLR signals such as LPS are able to trigger proinflammatory cytokine secretion by DCs, including Th1-polarizing IL-12. Here, we explored the murine Leishmania major infection model to examine the $CD4^{+}$ T cell response induced by differentially matured DCs. When partially matured TNF-DCs were injected into BALB/c mice before infection, the mice failed to control L. major infection and developed a Th2 response which was dependent on IL-4Rα signaling. In contrast, injections of fully matured LPS+CD40-DCs induced a Th1 response controlling the infection. Pulsing DCs with a lysate of L. major did not affect DC maturation with TNF-α or LPS+anti-CD40. When the expression of different Notch ligands on DCs was analyzed, we found increased expression of Th2-promoting Jagged2 in TNF-DCs, whereas LPS+CD40-DCs up-regulated the Th1-inducing Delta4 and Jagged1 molecules. The Th2 polarization induced by TNF-DCs required interaction with CD1d-restricted NKT cells. However, NKT cell activation by L. major lysate-pulsed DCs was not affected by blockade of the endogenous glycolipid, suggesting exchange with exogenous parasite-derived CD1 glycolipid Ag. In sum, the differentiation stage of DCs as well as their interaction with NKT cells determines Th1/Th2 differentiation. These results have generic implications for the understanding of DC-driven Th cell responses and the development of improved DC vaccines against leishmaniasis. |
| Ending Page | 4381 |
| Page Count | 11 |
| Starting Page | 4371 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.180.7.4371 |
| Journal | The Journal of Immunology |
| Issue Number | 7 |
| Volume Number | 180 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2008-04-01 |
| Access Restriction | Open |
| Subject Keyword | Differentiation Stage Cells Determine Th1/th2 Nkt Cells Determine Interaction with Nkt Determine Th1/th2 Differentiation Cells Determines |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
