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Alveolar macrophage-derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes.

Goritzka M, Makris S, Kausar F, Durant LR, Pereira C, Kumagai Y, Culley FJ, Mack M, Akira S, Johansson C - J. Exp. Med. (2015)

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.

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Affiliation: Centre for Respiratory Infection, Respiratory Infections Section, National Heart and Lung Institute, Imperial College London, London W2 1PG, England, UK.

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AMs are the main producers of type I IFNs in lungs of RSV-infected mice. (A) Lung cells from naive C57BL/6 mice or 4 and 12 h after RSV infection were sorted into CD45− and CD45+ fractions. Expression of Ifna5 and Ifnb mRNA was assessed by quantitative RT-PCR. One representative experiment of three is shown using pooled cells from five mice for each time point. (B) Lung leukocyte populations from Ifna6gfp/+ mice at 18 h after RSV infection were sorted into GFP+ and GFP− AMs (Siglec-FhiCD11chi), CD103+ DCs (CD11chiCD11bloCD103hi), CD11b+ DCs (CD11chiCD11bhiCD64loLy6Clo), pDCs (CD11cintCD11bloB220hiSiglec-Hhi), moDCs (CD11bhiCD64hiCD11chi), infMos (CD11bhiCD64hiCD11clo), and neutrophils (CD11bhiLy6Ghi). Expression of Ifna5 and Ifnb mRNA was assessed by quantitative RT-PCR. Each point depicts data from an individual experiment (two to three) with cells sorted from pools of 25–40 mice per experiment. The symbols represent different cell types as indicated, and the horizontal bars represent the mean.
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fig2: AMs are the main producers of type I IFNs in lungs of RSV-infected mice. (A) Lung cells from naive C57BL/6 mice or 4 and 12 h after RSV infection were sorted into CD45− and CD45+ fractions. Expression of Ifna5 and Ifnb mRNA was assessed by quantitative RT-PCR. One representative experiment of three is shown using pooled cells from five mice for each time point. (B) Lung leukocyte populations from Ifna6gfp/+ mice at 18 h after RSV infection were sorted into GFP+ and GFP− AMs (Siglec-FhiCD11chi), CD103+ DCs (CD11chiCD11bloCD103hi), CD11b+ DCs (CD11chiCD11bhiCD64loLy6Clo), pDCs (CD11cintCD11bloB220hiSiglec-Hhi), moDCs (CD11bhiCD64hiCD11chi), infMos (CD11bhiCD64hiCD11clo), and neutrophils (CD11bhiLy6Ghi). Expression of Ifna5 and Ifnb mRNA was assessed by quantitative RT-PCR. Each point depicts data from an individual experiment (two to three) with cells sorted from pools of 25–40 mice per experiment. The symbols represent different cell types as indicated, and the horizontal bars represent the mean.

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.


Alveolar macrophage-derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes.

Goritzka M, Makris S, Kausar F, Durant LR, Pereira C, Kumagai Y, Culley FJ, Mack M, Akira S, Johansson C - J. Exp. Med. (2015)

AMs are the main producers of type I IFNs in lungs of RSV-infected mice. (A) Lung cells from naive C57BL/6 mice or 4 and 12 h after RSV infection were sorted into CD45− and CD45+ fractions. Expression of Ifna5 and Ifnb mRNA was assessed by quantitative RT-PCR. One representative experiment of three is shown using pooled cells from five mice for each time point. (B) Lung leukocyte populations from Ifna6gfp/+ mice at 18 h after RSV infection were sorted into GFP+ and GFP− AMs (Siglec-FhiCD11chi), CD103+ DCs (CD11chiCD11bloCD103hi), CD11b+ DCs (CD11chiCD11bhiCD64loLy6Clo), pDCs (CD11cintCD11bloB220hiSiglec-Hhi), moDCs (CD11bhiCD64hiCD11chi), infMos (CD11bhiCD64hiCD11clo), and neutrophils (CD11bhiLy6Ghi). Expression of Ifna5 and Ifnb mRNA was assessed by quantitative RT-PCR. Each point depicts data from an individual experiment (two to three) with cells sorted from pools of 25–40 mice per experiment. The symbols represent different cell types as indicated, and the horizontal bars represent the mean.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4419339&req=5

fig2: AMs are the main producers of type I IFNs in lungs of RSV-infected mice. (A) Lung cells from naive C57BL/6 mice or 4 and 12 h after RSV infection were sorted into CD45− and CD45+ fractions. Expression of Ifna5 and Ifnb mRNA was assessed by quantitative RT-PCR. One representative experiment of three is shown using pooled cells from five mice for each time point. (B) Lung leukocyte populations from Ifna6gfp/+ mice at 18 h after RSV infection were sorted into GFP+ and GFP− AMs (Siglec-FhiCD11chi), CD103+ DCs (CD11chiCD11bloCD103hi), CD11b+ DCs (CD11chiCD11bhiCD64loLy6Clo), pDCs (CD11cintCD11bloB220hiSiglec-Hhi), moDCs (CD11bhiCD64hiCD11chi), infMos (CD11bhiCD64hiCD11clo), and neutrophils (CD11bhiLy6Ghi). Expression of Ifna5 and Ifnb mRNA was assessed by quantitative RT-PCR. Each point depicts data from an individual experiment (two to three) with cells sorted from pools of 25–40 mice per experiment. The symbols represent different cell types as indicated, and the horizontal bars represent the mean.
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.

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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre for Respiratory Infection, Respiratory Infections Section, National Heart and Lung Institute, Imperial College London, London W2 1PG, England, UK.

Show MeSH
Related in: MedlinePlus