poly IC interacts with the macrophage scavenger receptor SR-A (gene Msr1) (protein also designated as CD204), which can deliver poly IC to intracellular TLRs via endocytosis.

ok, thanks, so Imiquimod or CpG are not recognized by CD204? or are they connected by some other less efficient mechanism? It will be a great help if you can share some key words related to recent development.

thanks again

Satheesh

Whereas imiquimod and CpGs induce type I + III IFNs selectively via TLR7 and TLR9 (via plasmacytoid dendritic cells) is poly IC seen either via TLR3 or dependent on the lenghts by the cytoplasmic RLHs Rig-I or MDA5.

Plasmacytoid DC do not express TLR3 or RLHs and thus ignore poly IC. TLR3 expressing hematopoietic cells produce minor amounts of IFN-I to poly IC. They also use the RLHs for IFN-I production. CD8+ cDCs ( in human BDCA3+ cDCs) produce large amount of IFN-lambda to poly IC (see Lauterbach et al J Exp Med 2010).

However, systemic levels of IFN-alpha to poly IC are mainly produced by non-hematopoietic cells (Gitlin et al. PNAS 2006; Longhi et al. J Exp Med 2009; Lauterbach et al. J Exp Med 2010)

Thank you Dr. Hubertus Hochrein.

that was very nice and clear explanation.

I am working on fish immunology, and hence there may be a difference in the expression pattern. In fishes, until today DCs are not found. In my experiment, I had stimulated kidney cells (primary hematopoietic organ) with Imiquimod and poly I:C and checked relative expression of PRRs, IRFs, IFN & ISGs.

As you had explained, I expected to get high type I IFN, RLRs and other downstream signalling, but I have got something different.

TLR 7 was increased both with imiquimod as well as poly I:C but TLR 3 only by poly IC. But MDA5 and LGP2 were increased by both where poly IC stimulated quicker and stronger.

IRF 3 and IRF 7 expression were much similar, but type I IFN is very low in imiquimod group.

Interestingly Mx level is was high in imiquimod group, though it was lesser compared to poly IC group.

All these results put me in puzzle, I have to repeat these with some fresh analysis, but thought to get some idea from experienced researchers to tackle this.

Thanks again,

Satheesh

SR-A (CD204) is expressed primarily in macrophages, but at also at low levels in nonhematopoietic cells see

DeWitte-Orr SJ, Collins SE, Bauer CM, Bowdish DM, Mossman KL. An accessory to

the 'Trinity': SR-As are essential pathogen sensors of extracellular dsRNA,

mediating entry and leading to subsequent type I IFN responses. PLoS Pathog. 2010

Mar 26;6(3):e1000829. PubMed PMID: 20360967; PubMed Central PMCID: PMC2847946.

The related MARCO binds CpG see: Józefowski S, Sulahian TH, Arredouani M, Kobzik L. Role of scavenger receptor

MARCO in macrophage responses to CpG oligodeoxynucleotides. J Leukoc Biol. 2006

Oct;80(4):870-9. Epub 2006 Aug 1. PubMed PMID: 16882874.

CD14 may also connect to intracellular TLRs

I do not know about imiquimod. Based on the structure it may gain entry through purinoriceptors or simly be membrane permeant

Good Luck

Dear Zissis Chroneos,

thank you for your suggestions and also the articles.