Cytokine Profiles of Human Myeloid Dendritic Cell Subsets in Response to RSV and TLR Agonists

Abstract

Dendritic cell (DC)-Respiratory Syncytial Virus (RSV) interactions determine the immunologic consequence of infection. Toll-like receptors (TLRs) convert pathogen recognition into signals controlling the outcome of immunity. How RSV responses are tailored by TLRs in human myeloid DC (mDC) subsets remains unknown. Identifying overlapping cytokine patterns induced by RSV and TLR agonists in each subset may help identify TLR pathways utilized by RSV. Using FACS sorting, mDC subsets (BDCA-1+ and BDCA-1-) were isolated from peripheral blood of healthy volunteers and incubated with RSV, Poly I:C (TLR3 agonist), LPS (TLR4 agonist), and ssRNA (TLR8 agonist). Two-way ANOVA was used to determine statistically significant differences in cytokine profiles induced by agonists between subsets and by RSV vs. TLR agonists in each subset. BDCA-1+ and BDCA-1- mDCs produced similar cytokine profiles in response to RSV (F=0.44,p=0.50) and ssRNA (F=0.0,p=0.99), but distinct cytokine profiles in response to Poly I:C (F=10.03,p=0.002) and LPS (F=7.14,p=0.008). Overlapping cytokine profiles were induced by RSV and Poly I:C (F=0.24,p= 0.63) in BDCA-1+ mDCs; and RSV and LPS (F=0.83,p=0.36) in BDCA-1- mDCs. These results suggest a common signaling pathway for RSV and Poly I:C (TLR3) in BDCA-1+; and RSV and LPS (TLR4) in BDCA-1- mDCs. The combination of cytokines produced in response to infection is TLR-specific. Thus, TLR signaling pathways utilized by RSV may have important implications in the outcome of resulting immune responses. To our knowledge, this is one of the first studies to identify potential TLR pathways activated by RSV in human mDC subsets.