| First Author | Tam MA | Year | 2009 |
| Journal | Immunology | Volume | 128 |
| Issue | 3 | Pages | 429-38 |
| PubMed ID | 20067542 | Mgi Jnum | J:162279 |
| Mgi Id | MGI:4818544 | Doi | 10.1111/j.1365-2567.2009.03128.x |
| Citation | Tam MA, et al. (2009) MyD88 and interferon-alpha/beta are differentially required for dendritic cell maturation but dispensable for development of protective memory against Listeria. Immunology 128(3):429-38 |
| abstractText | Signalling pathways mediated by MyD88 are important for sensing Toll-like receptor (TLR) ligands and directing an immune response. However, the influence of MyD88-derived cytokines and interferon (IFN)-alpha/beta, the latter being made by both MyD88-dependent and -independent pathways, in phenotypic and functional dendritic cell (DC) maturation during infection is poorly understood. Here we investigate the contribution of MyD88-dependent and -independent pathways to DC maturation, CD8 T-cell activation and the generation of protective memory against Listeria monocytogenes. We show that neither MyD88 deficiency alone nor MyD88/IFN-alphabetaR double deficiency alters Listeria-induced costimulatory molecule up-regulation on DCs in vivo. In contrast, DCs from infected IFN-alphabetaR(-/-) mice had higher CD80 and CD86 expression than wild-type DCs. We then examined the function of DCs matured in infected knockout mice. We found that DCs from Listeria-infected MyD88(-/-) and MyD88(-/-) IFN-alphabetaR(-/-) mice induced little or no IFN-gamma by CD8 T cells, respectively. In contrast, DCs from infected IFN-alphabetaR(-/-) mice had a greater capacity to induce IFN-gamma compared with DCs from infected wild-type mice. When the CD8 T-cell memory response was analysed, infected MyD88(-/-) and MyD88(-/- )IFN-alphabetaR(-/-) mice were found to have fewer bacteria-specific memory CD8 T cells than wild-type mice. However, the fraction of bacteria-specific CD8 T cells making IFN-gamma was similar in all mouse strains, and MyD88(-/-) and MyD88(-/- )IFN-alphabetaR(-/-) mice survived lethal challenge. Together the data suggest an inhibitory effect of IFN-alpha/beta on functional DC maturation during Listeria infection and reveal overlapping roles of MyD88-induced cytokines and IFN-alpha/beta in DC maturation and protective anti-Listeria immunity. |
