TLR7 Is for Bacteria, Too

Science Signaling  26 May 2009:
Vol. 2, Issue 72, pp. ec174
DOI: 10.1126/scisignal.272ec174

The type I interferons (IFNs) IFN-α and IFN-β are produced as part of the innate immune response to the presence of microbial products early in infection. Although the role of type I IFNs in antiviral responses is well studied, these cytokines also modulate immune responses to nonviral pathogens, including bacteria; however, how bacteria trigger IFN production is unclear. Given that different cell types use either cytosolic or endosomal components to respond to viral products, Mancuso et al. investigated whether the subcellular localization of whole bacteria in cells of the innate immune system might affect their ability to induce type I IFN production. The authors found that conventional dendritic cells (cDCs) and macrophages, but not plasmacytoid DCs (pDCs), produced type I IFNs in response to phagosomal bacteria and cytosolic bacteria; however, cDCs produced the greatest quantities. In cDCs, IFN production in response to phagosomal, but not cytosolic, bacteria was dependent on Toll-like receptor 7 (TLR7), its adaptor protein MyD88, and the transcription factor interferon regulatory factor 1 (IRF1), whereas IFN production in response to cytosolic bacteria was dependent on IRF3. Immunofluorescence microscopy showed the colocalization of phagosomal bacterial products and TLR7 pathway components in phagolysosomal compartments. Mice deficient in TLR7 or IRF1 were more susceptible than wild-type (WT) mice to infection with phagosomal bacteria. In vitro experiments showed that cDCs from WT mice, but not TLR7-deficient mice, produced type I IFNs in response to bacterial RNA. Together these data provide evidence for a cell type–specific response to bacterial infection that depends on the subcellular localization of the invading organisms.

G. Mancuso, M. Gambuzza, A. Midiri, C. Biondo, S. Papasergi, S. Akira, G. Teti, C. Beninati, Bacterial recognition by TLR7 in the lysosomes of conventional dendritic cells. Nat. Immunol. 10, 587–594 (2009). [PubMed]