| First Author | Banerjee P | Year | 2008 |
| Journal | Int Immunol | Volume | 20 |
| Issue | 12 | Pages | 1551-63 |
| PubMed ID | 18931363 | Mgi Jnum | J:143565 |
| Mgi Id | MGI:3828193 | Doi | 10.1093/intimm/dxn114 |
| Citation | Banerjee P, et al. (2008) Porin-incorporated liposome induces Toll-like receptors 2- and 6-dependent maturation and type 1 response of dendritic cell. Int Immunol 20(12):1551-63 |
| abstractText | Porin of Shigella dysenteriae was incorporated in liposome (PIL) and presented to mouse splenic dendritic cells (DC). PIL up-regulated Toll-like receptor (TLR) 2 and TLR6 on DC, showing that co-expression of the two TLRs is involved in recognition of porin. Detection of myeloid differentiating factor 88 (MyD88)-TLR2 complex confirmed interaction between the two for triggering the downstream signaling, which ultimately led to TLR2-dependent nuclear translocation of nuclear factor-kappa B. PIL-induced expression of MHC class II (I-Ab), CD40 and CD80 showed maturation of DC, whereas up-regulation of intercellular adhesion molecule-1 and CCR7 implicated the capacity of splenic DC to migrate. Induction of messenger ribonucleic acid for the chemokines, macrophage-inflammatory protein (MIP)-1alpha, MIP-1beta and regulated upon activation, normal T cell expressed and secreted indicated a strong bias of PIL for type 1 polarization that was supported by the intracellular expression and release of tumor necrosis factor (TNF)-alpha and IL-12. Along with CD40 and CD80 expression, release of the cytokines of CD11c+ JAWS II cells was inhibited by TLR2 or simultaneous TLR2 and 6 knockdown showing that recognition of PIL by the two TLRs is essential for DC activation and type 1 polarization. The signaling pathway initiated upon recognition of PIL by the TLRs was MyD88 dependent as confirmed by inhibition of IL-6, TNF-alpha and IL-12 release of MyD88-knockdown JAWS II cells. The maturation and polarization of DC induced T(h)1 phenotype, as evident from proliferation, activation and IFN-gamma release of allogeneic CD4+ T cells in response to PIL-stimulated DC, thereby suggesting that the adjuvant activity of PIL can successfully bridge the innate and adaptive immunity. |
