Age-related differences in the lung tissue susceptibility to Respiratory Syncytial Virus

Poster - Session 1International audienceThe high incidence of acute lower respiratory tract infections (ALRI) in infants likely relates to the immaturity of the neonatal pulmonary immune system. Respiratory syncytial virus (RSV), a paramyxovirus, is the most frequently encountered virus in severe ALRI, during early infancy. The immune mechanisms associated with this higher susceptibility are still largely unknown. Our objective was to assess age-related differences in the lung susceptibility to RSV in lambs as a model for the veterinary (calves) and human pathology: lambs are susceptible to bovine RSV, and preterm lambs develop more severe ALRI, just like preterm infants. Besides lamb is a widely-used model for studies concerning respiratory deficiencies of preterm infants, as infant and lamb have a similar pulmonary development. We collected samples of tracheal, lung and mediastinal lymph node tissue from either preterm lambs or from 1 week to 9 month-old lambs. We first looked at Toll-Like Receptors (TLR) and Protease-Activated Receptors (PAR) mRNA expression, as early mediators of inflammation and antiviral defenses. Depending on the tissue, we found differential mRNA expression for both PAR and TLR, whereas age variations were mainly observed for TLR3, 7 and 9 expressions. Because TLR are mostly expressed by dendritic cells (DC), we next characterized conventional DC subsets in the lung by FACS according to age. Thus, we demonstrated age-related differences on major receptors involved in antiviral defenses. To prove that it contributes to newborn susceptibility to RSV, we are now developing a model of lung explants culture to analyze gene expression during RSV infection