Dendritic cell differentiation state and their interaction with NKT cells determine Th1/Th2 differentiation in the murine model of Leishmania major infection. Export

@article{citeulike:3432082, abstract = {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-4Ralpha 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-alpha 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.}, author = {Wiethe, C. and Debus, A. and Mohrs, M. and Steinkasserer, A. and Lutz, M. and Gessner, A.}, citeulike-article-id = {3432082}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/18354157}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=18354157}, issn = {0022-1767}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, keywords = {dendritic, leishmania, mice, nkt-cells, polarization, superlist, th1, th2, thelist}, month = {April}, number = {7}, pages = {4371--4381}, posted-at = {2008-10-21 04:07:17}, priority = {2}, title = {Dendritic cell differentiation state and their interaction with NKT cells determine Th1/Th2 differentiation in the murine model of Leishmania major infection.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/18354157}, volume = {180}, year = {2008} }

TY - JOUR ID - citeulike:3432082 L3 - citeulike-article-id:3432082 N2 - 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-4Ralpha 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-alpha 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. IS - 7 JF - Journal of immunology (Baltimore, Md. : 1950) SN - 0022-1767 EP - 4381 TI - Dendritic cell differentiation state and their interaction with NKT cells determine Th1/Th2 differentiation in the murine model of Leishmania major infection. VL - 180 SP - 4371 KW - dendritic KW - leishmania KW - mice KW - nkt-cells KW - polarization KW - superlist KW - th1 KW - th2 KW - thelist AU - Wiethe, C AU - Debus, A AU - Mohrs, M AU - Steinkasserer, A AU - Lutz, M AU - Gessner, A PY - 2008/04/01/ UR - http://view.ncbi.nlm.nih.gov/pubmed/18354157 ER -