If mRNA would get into the endosomes of human cells would it be recognized by TLR7/8? And if it would be recognized, would it be immunostimulatory, or does the 5' cap and 3' poly A-tail prevent that reactions toward self RNA occur?
I'd say so! The natural ligands of TLR 7 and TLR 8 are known to be ssRNA. This study right here (http://www.ncbi.nlm.nih.gov/pubmed/14976262) shows that HIV-derived ssRNA stimulated interferon production from innate cells, in a TLR7/8 dependent manner. So, yeah, I'd agree that mRNA would be immunostimulatory.
Hope this helps! :)
A.
Maybe... depends on cap and modifications as well. I know that TLR13 is not expressed in humans, as far as we know right now. But read up on it's agonists.
As per as I understand TLR , it shouldn't. TLR7/8 responds to viral SSRNA which made some hypothesize that it must react to small ncRNAs as well. It seemed later that TLR7/8 only responds to the siRNAs that have higher CpG ratio. mRNA shouldn't invoke any such reaction.
Think so too. SiRNA is immunostimulating pDc via TLR7. Apoptotic bodies that contain mRNA activates pDC...
don't forget that, stimulation of TLR depends also of consensus sequence of rna.
I have tried transfection of cellular RNA into 293T cells by lipofectamine, the cellular RNA did not stimulate the cells to produce IFN. the transfection of RNA by lipofectamine may directly deliver the RNA into cytoplasm that avoid to be recognized by TLRs.