Infection of nonclassic monocytes by respiratory syncytial virus induces an imbalance in the CD4 T-cell subset response.

Respiratory syncytial virus (RSV) causes lower respiratory tract infections in infants and young children, leading to a pathogenesis-associated imbalance in CD4 T-cell subsets and monocyte subsets. To investigate whether RSV affects the imbalance of CD4 T-cells through monocytes, we examined the effects of the RSV-infected monocyte subset on CD4 T-cell subsets, namely, Th1, Th2, Th17, and regulatory T (Treg) subsets, on proliferation and identified key monocyte-derived cytokines. We found that RSV efficiently infects CD16 monocytes, but not CD16 monocytes, cocultures of CD4 T-cells with RSV-infected CD16 monocytes, inhibits Treg cell proliferation and increases Th2 cell frequency, suggesting that RSV causes an imbalance in the CD4 T-cell subset by primarily infecting CD16 monocytes. Our data also revealed that IL-1β and IL-10 are key cytokines responsible for the activities of RSV-infected CD16 monocytes. In a mouse model, we found that high-efficiency RSV infection of mouse Ly6C monocytes, corresponding to CD16 monocytes in humans, and adoptive transfer of Ly6C monocytes during RSV infection decreased the Treg frequency in the lungs and aggravated pneumonia. Our data indicate that RSV can increase its pathogenesis through infection of nonclassic monocytes, leading to a CD4 T-cell imbalance.IMPORTANCEThis study identified a pathogenesis pathway related to the RSV-nonclassic monocyte-IL-1β/IL-10-CD4 T-cell subset balance, which links the heterogeneity of monocytes to RSV pathogenesis and elucidates a new mechanism by which RSV infection disrupts the balance of CD4 T cells during RSV infection. These new findings provide potential therapeutic targets for RSV infection.