Miniature lungs: the road towards a better model to study RSV disease

Sachs N, Papaspyropoulos A, Zomer-van Ommen DD, Heo I, Böttinger L, Klay D, Weeber Huelsz-Prince FG, Iakobachvili N, Amatngalim GD, Ligt  de J , Hoeck van A , Proost N, Viveen MC, Lyubimova A, Teeven L, Derakhshan S, Korving J, Begthel H, Dekkers JF, Kumawat K, Ramos E, Oosterhout van MFM, Offerhaus GJ, Wiener DJ,  Olimpio EP, Dijkstra KK, Smit EF, Linden van der M, Jaksani S, Ven van de M, Jonkers J , Rios AC, Voest EE, Moorsel van CHM, Ent van der CK, Cuppen E , Oudenaarden van A, Coenjaerts FE, Meyaard L, Bont LJ, Peters PJ, Tans SJ, Zon van JS, Boj SF, Vries RG, Beekman JM & Clevers H.

Summary:
Sachs from UMC Utrecht developed human airway organoids (miniature lungs) that offer the possibility to study RSV in an human in vitro model. The authors show that RSV replicates well in human airway organoids and that infection can be inhibited after pre-treatment with palivizumab. Furthermore, RSV caused epithelial changes that mimic disease characteristics such as epithelial shedding, syncytia formation and alterations of the cytoskeleton.  Also, there was an upregulation of antiviral genes and an enhanced secretion of cytokines such as IP-10. Both of these findings reflect the immune responses following RSV infection in infants.  Lastly, human airway organoids offer the possibility to study the interaction between immune cells and the RSV infected epithelium. The latter is of major importance to increase the knowledge on RSV immune signalling.
Altogether, RSV – infected airway organoids offer the possibility to study numerous aspects of RSV disease, including airway remodelling, immune cell interaction and treatment possibilities.
Written by Sjanna Besteman

Paper of the month | February 2019