Pulmonary Susceptibility of Neonates to Respiratory Syncytial Virus Infection: A Problem of Innate Immunity?

Figure 2

Immediate immune responses of pulmonary resident cells to RSV infection in neonates. Servier Medical Art has provided images. Neonatal RSV exposure leads to an early IL-33 secretion by respiratory epithelial cells [96]. IL-33 signals through its receptor ST2 localized at the membrane of ILC2. This alarmin supports the increase in the ILC2 number and IL-13 production in the lungs of RSV-infected neonatal mice [74]. ILC2 can promote a switch towards a type 2 phenotype for AMs or lung DCs at a steady state or in a house dust mite-induced asthma model [27, 30]. Concerning the IFN-I pathway, neonatal pDCs display a poor pulmonary mobilization and a weak activation of the IFN-I pathway following RSV infection [29]. AMs are the main source of IFN-I in RSV-infected adult lungs, but the question remains open during the neonatal period [54]. Therefore, it is strongly suspected that ILC2 cells are indirectly responsible for the inability of neonatal mice to mount an effective IFN-I response to counteract RSV infection. In addition, IL-10-secreting nBregs may constitute another cellular subset contributing to the type 2 immunity induced by RSV infection in neonates [40, 99].