Bone marrow plasmacytoid dendritic cells can differentiate into myeloid dendritic cells upon virus infection

Abstract

Two subsets of dendritic cell (DCs), plasmacytoid (p) and myeloid (m) DCs, have been described in humans and mice. These subsets are known to have divergent roles during an immune response, but their developmental course is unclear. Here we report that virus infection induces bone marrow pDCs to differentiate into mDCs, thereby undergoing profound phenotypic and functional changes including the acquisition of enhanced antigen-presenting capacity and the ability to recognize different microbial structures through Toll-like receptor 4. The conversion of pDCs into mDCs is also induced by the injection of double-stranded RNA and requires type I interferons. Our results establish a precursor-product developmental relationship between these two DC subsets and highlight unexpected plasticity of bone marrow pDCs.

Type I interferon regulates pDC maturation and Ly49Q expression

“…A subset of Ly49Q -, but not Ly49Q + , pDC partially differentiate into cDC after poly(I:C) injection Zuniga et al [15] reported that virus infection induces bone marrow pDC to differentiate into cDC. Because numbers of Ly49Q -pDC increase in the bone marrow in response to viral infection, we hypothesized that Ly49Q -, but not Ly49Q + , pDC are responsible for differentiation into cDC.…”

“…It has been suggested by Zuniga et al [15] that type I IFN is one of the key regulators of pDC development. Here, we found that type I IFN prevents the acquisition of Ly49Q that normally occurs in Ly49Q -pDC from bone Figure 3.…”

“…Kreisel et al [45] reported that cDC can be generated from CD31 high /Ly6C -, CD31 + / Ly6C + , and CD31 -/Ly6C high bone marrow subpopulations, but pDC could only be derived from the CD31 high / Ly6C -subset. Zuniga et al [15] reported that bone marrow pDC acquired the ability to become cDC but not peripheral pDC after viral infection. Our results support this conclusion.…”

“…Zuniga et al [15] recently showed that type I IFN negatively regulate pDC maturation during viral infection, and others [16] have reported that IFN control chemokine expression patterns that lead pDC to inflamed lymph nodes [17].…”

“…We found that type I IFN are actually produced by the bone marrow cells cultured in the presence of FMS-like tyrosine kinase 3 ligand (Flt3L), and partially inhibit Ly49Q acquisition in vitro. Since another group [15] reported that virus infection induces bone marrow pDC to differentiate into cDC, we also compared the abilities of Ly49Q -and Ly49Q + pDC to differentiate into cDC after TLR stimulation.…”