Human metapneumovirus infection induces expression of thymic stromal lymphopoetin and IL-33 in airway epithelial cells in vitro and lung infiltration of OX40L+ DCs in vivo (P6200)

Abstract

Abstract Human metapneumovirus (hMPV) is a common virus known to induce acute respiratory tract infection. The specific mechanism by which hMPV modulates the immune response in infected airway epithelial cells (AECs) leading to tissue damage, still remains unknown. Thymic stromal lymphopoetin (TSLP) and IL-33, epithelial cell derived cytokines, induce high expression levels of OX40L on DCs, leading to Th2 responses and allergic inflammation. Recent reports have shown that Th2 inflammatory responses in RSV infections are mediated by TSLP-dependent OX40L expression in DCs. We hypothesize that the TSLP, IL-33 and OX40L pathway mediates lung inflammation in hMPV-infected individuals. We tested the expression of TSLP and IL-33 in human AECs after hMPV infection and compared them with RSV-infected AECs by qRT-PCR. We also evaluated lung infiltration of GR1+CD11b+ and CD11c+CD11b+OX40L+ cells in hMPV-infected mice by flow cytometry. We found an induction of TSLP mRNA levels in hMPV-infected AECs in a MOI dependent-manner. We also proved that hMPV induces higher TSLP mRNA levels than RSV in AECs, and hMPV but not RSV up-regulates IL-33 levels in AECs. Furthermore, we showed that hMPV infection in mice induces an increased lung infiltration of neutrophiles and OX40L+ DCs than the mock control group. These results suggest that hMPV infection in lungs may be inducing an augmented Th2 inflammatory response, through TSLP and IL-33 produced by hMPV-infected AECs and activated DCs expressing OX40L.