Alveolar macrophage-derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes.
Bottom Line: AMs detect RSV via mitochondrial antiviral signaling protein (MAVS)-coupled retinoic acid-inducible gene 1 (RIG-I)-like receptors (RLRs), and loss of MAVS greatly compromises innate immune restriction of RSV.Thus, infMo recruitment constitutes an important and hitherto underappreciated, cell-extrinsic mechanism of type I IFN-mediated antiviral activity.Dysregulation of this system of host antiviral defense may underlie the development of RSV-induced severe lung inflammation.
Affiliation: Centre for Respiratory Infection, Respiratory Infections Section, National Heart and Lung Institute, Imperial College London, London W2 1PG, England, UK.Show MeSH
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Mentions: To independently validate these findings and measure additional type I IFN species, CD45− and CD45+ cells from naive or infected lungs from C57BL/6 mice were purified by cell sorting, and the levels of Ifna5 and Ifnb mRNA were determined by quantitative RT-PCR (Fig. 2 A; for gating see Fig. S1 B). Concordant with the earlier results in Fig. 1, CD45− stromal cells expressed limited amounts of Ifna5 and Ifnb when compared with CD45+ cells (Fig. 2 A). To distinguish among the latter, different lung leukocyte cell populations were purified by cell sorting from infected Ifna6gfp/+ mice (for gating strategy see Fig. S1, A and B). As expected, GFP+ AMs contained the highest levels of Ifna5 and Ifnb transcripts (Fig. 2 B). Low levels could also be detected in GFP− AMs and pDCs, arguing for slight underreporting in Ifna6gfp/+ mice. In conclusion, AMs account for the majority of type I IFN production in the lungs of RSV-infected mice with only a minor contribution from pDCs.
Affiliation: Centre for Respiratory Infection, Respiratory Infections Section, National Heart and Lung Institute, Imperial College London, London W2 1PG, England, UK.