Figure 1.

A simplified model of the potential contributions of selective sensors and cell types to IFN production during viral infections. Different innate immune recognition receptors are involved in sensing various types of viral nucleic acids in distinct categories of cells during viral infections, which may promote different types of anti-viral defenses. For each selected sensor shown, the types of viral nucleic acids recognized and the downstream signaling cascade induced are represented in a simplified, schematic manner. The potential specific role of each cell type in anti-viral defenses is also indicated at the bottom of each panel. (A) Potentially all types of infected cells can detect endogenous viral replication through cytosolic sensors triggering their local production of IFN-β/λ to control viral replication in an autocrine and paracrine fashion in infected tissues. (B) Uninfected XCR1⁺ DCs selectively produce high levels of IFN-λ and IFN-β upon engulfment of materials containing dsRNA and the consecutive triggering of TLR3 in endosomes. The receptor of IFN-λ is mostly expressed by epithelial cells. Hence, XCR1⁺ DCs might be involved in inducing local IFN responses in virally infected epithelial tissues. Since XCR1⁺ DCs are especially efficient at producing IFN-III upon HCV stimulation, they might contribute to local or systemic IFN production during infection with this virus, to promote IFN-λ-mediated protection of hepatocytes. Uninfected XCR1⁺ DCs and other uninfected cells may produce some IFN-β upon engulfment of materials containing ssRNA and the consecutive triggering of TLR8 in endosomes. The contribution of this pathway to anti-viral defense is not well understood yet, in part because mouse TLR8 is deficient for this function. (C) Uninfected pDCs selectively produce high levels of all subsets of IFNs upon engulfment of materials containing ssRNA or CpG DNA and the consecutive triggering of TLR7/9 in endosomes. However, pDCs seem to be activated for this function only in lymphoid tissues. Hence, pDC might contribute to systemic IFN production during blood-borne viral infections or as a failsafe mechanism activated upon abnormal widespread dissemination of a viral infection once it has escaped local confinement at its portal of entry. CM, cell membrane; NM, nuclear membrane.