| First Author | Weiss G | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 6 | Pages | 2860-8 |
| PubMed ID | 22896628 | Mgi Jnum | J:189947 |
| Mgi Id | MGI:5447275 | Doi | 10.4049/jimmunol.1103491 |
| Citation | Weiss G, et al. (2012) MyD88 drives the IFN-beta response to Lactobacillus acidophilus in dendritic cells through a mechanism involving IRF1, IRF3, and IRF7. J Immunol 189(6):2860-8 |
| abstractText | Type I IFNs are induced by pathogens to protect the host from infection and boost the immune response. We have recently demonstrated that this IFN response is not restricted to pathogens, as the Gram-positive bacterium Lactobacillus acidophilus, a natural inhabitant of the intestine, induces high levels of IFN-beta in dendritic cells. In the current study, we investigate the intracellular pathways involved in IFN-beta upon stimulation of dendritic cells with L. acidophilus and reveal that this IFN-beta induction requires phagosomal uptake and processing but bypasses the endosomal receptors TLR7 and TLR9. The IFN-beta production is fully dependent on the TIR adapter molecule MyD88, partly dependent on IFN regulatory factor (IRF)1, but independent of the TIR domain-containing adapter inducing IFN-beta MyD88 adapter-like, IRF and IRF7. However, our results suggest that IRF3 and IRF7 have complementary roles in IFN-beta signaling. The IFN-beta production is strongly impaired by inhibitors of spleen tyrosine kinase (Syk) and PI3K. Our results indicate that L. acidophilus induces IFN-beta independently of the receptors typically used by bacteria, as it requires MyD88, Syk, and PI3K signaling and phagosomal processing to activate IRF1 and IRF3/IRF7 and thereby the release of IFN-beta. |
