| First Author | Thomas PG | Year | 2005 |
| Journal | J Immunol | Volume | 175 |
| Issue | 4 | Pages | 2082-90 |
| PubMed ID | 16081774 | Mgi Jnum | J:107518 |
| Mgi Id | MGI:3621348 | Doi | 10.4049/jimmunol.175.4.2082 |
| Citation | Thomas PG, et al. (2005) A helminth glycan induces APC maturation via alternative NF-kappa B activation independent of I kappa B alpha degradation. J Immunol 175(4):2082-90 |
| abstractText | Activation of APCs via TLRs leads to activation of NF-kappaB, a key transcription factor in cells of the immune system most often associated with induction of Th1-type and proinflammatory responses. The neoglycoconjugate lacto-N-fucopentaose III (12-25 molecules)-dextran (LNFPIII-Dex) activates dendritic cells (DCs) via TLR4, as does LPS. However, unlike LPS, LNFPIII-Dex-activated cells induce Th2-type CD4+ T cell responses. This observation led us to ask whether LNFPIII-activated APCs were differentially activating NF-kappaB, and if so, could this partly account for how DCs mature in response to these two different pathogen-associated molecular patterns (PAMPs). In this study, we show that LNFPIII-Dex stimulation of APCs induces rapid, but transient NF-kappaB translocation and activity in the nucleus, in comparison with the persistent activation induced by LPS. We then demonstrate that transient vs persistent NF-kappaB activation has important implications in the development of the APC phenotype, showing that the second wave of NF-kappaB translocation in response to LPS is required for production of the proinflammatory mediator NO. In contrast to LPS, LNFPIII-stimulated APCs that only transiently activate NF-kappaB do not induce degradation of the known IkappaB family members or production of NO. However, cells stimulated with LNFPIII rapidly accumulate p50, suggesting that an alternative p105 degradation-dependent mechanism is primarily responsible for NF-kappaB activation downstream of LNFPIII. Finally, we show that while NF-kappaB translocation in LNFPIII-stimulated APCs is transient, it is required for the development of the DC 2 phenotype, confirming a crucial and multifaceted role for NF-kappaB in innate immune responses. |
