Critical role of the Toll-like receptor signal adaptor protein MyD88 in acute allograft rejection
AUTOR(ES)
Goldstein, Daniel R.
FONTE
American Society for Clinical Investigation
RESUMO
The Toll-like receptors (TLRs) are recently discovered germline-encoded receptors on APCs that are critically important in innate immune recognition of microbial pathogens. However, their role in solid-organ transplantation is unknown. To explore this role, we employed a skin allograft model using mice with targeted deletion of the universal TLR signal adaptor protein, MyD88. We report that minor antigen–mismatched (HY-mismatched) allograft rejection cannot occur in the absence of MyD88 signaling. Furthermore, we show that the inability to reject these allografts results from a reduced number of mature DCs in draining lymph nodes, leading to impaired generation of anti–graft-reactive T cells and impaired Th1 immunity. Hence, this work demonstrates that TLRs can be activated in a transplant setting and not solely by infections. These results link innate immunity to the initiation of the adaptive alloimmune response.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=155048Documentos Relacionados
- An Oligomeric Signaling Platform Formed by the Toll-like Receptor Signal Transducers MyD88 and IRAK-4*
- Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling
- Involvement of CD14, Toll-Like Receptors 2 and 4, and MyD88 in the Host Response to the Fungal Pathogen Cryptococcus neoformans In Vivo
- Drosophila MyD88 is an adapter in the Toll signaling pathway
- Both Innate Immunity and Type 1 Humoral Immunity to Streptococcus pneumoniae Are Mediated by MyD88 but Differ in Their Relative Levels of Dependence on Toll-Like Receptor 2