Editors' ChoiceInnate Immunity

Toll 2 Interferon Production

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Science Signaling  27 Oct 2009:
Vol. 2, Issue 94, pp. ec343
DOI: 10.1126/scisignal.294ec343

Recognition of microbial nucleic acids, lipids, and proteins by Toll-like receptors (TLRs) triggers immune responses. The major antiviral immune response is the induction of type I interferon, a response generally believed to occur after activation of TLRs that sense viral nucleic acids such as TLR3, TLR7, and TLR9 (see Bauernfeind and Hornung). However, some viruses produce proteins that activate TLR2, a TLR that had not been linked to interferon production. Barbalat et al. found that production of type I interferon (IFN) by bone marrow cells in response to the DNA virus vaccinia required TLR2 but not TLR9; further analysis showed that production of IFN-β and IFN-α4 was TLR2-dependent. 3d mice (which can respond to ligands that activate TLR2 and TLR4 but not to those activating TLR3, TLR7, or TLR9) produced interferon in response to vaccinia virus but not CpG oligodeoxynucleotide (CpG), thus demonstrating an alternate trigger for type I interferon production that is independent of nucleic acid sensing. IFN-β reporter mice in which activation of the IFN-β promoter produces yellow fluorescent protein (YFP) (MOB mice) showed YFP fluorescence in bone marrow and the spleen after exposure to vaccinia virus (but not to CpG). Analysis of cell surface markers indicated that CD11b+ cells, and more specifically inflammatory monocytes, in bone marrow and spleen were responsible for type I interferon production in response to vaccinia virus. CD11b-DTR mice injected with diphtheria toxin to deplete inflammatory monocytes showed reduced production of type I interferon and increased titers of vaccinia virus compared to mice injected with vehicle. The authors propose that TLR2 may recognize certain viral proteins with conserved functions and structures, such as the fusion apparatus that is required for viral propagation.

R. Barbalat, L. Lau, R. M. Locksley, G. M. Barton, Toll-like receptor 2 on inflammatory monocytes induces type I interferon in response to viral but not bacterial ligands. Nat. Immunol. 10, 1200–1207 (2009). [PubMed]

F. Bauernfeind, V. Hornung, TLR2 joins the interferon gang. Nat. Immunol. 10, 1139–1141 (2009). [PubMed]

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