In vivo conversion of BM plasmacytoid DC into CD11b+ conventional DC during virus infection.
DC are a highly heterogeneous population that plays a critical role in host defense. We previously demonstrated that virus infection induces BM plasmacytoid DC (pDC) differentiation into CD11b(+) conventional DC (cDC) upon in vitro culture with Fms-like tyrosine kinase 3 ligand (Flt3L). Here we use immunoglobulin D-J rearrangements and pDC adoptive transfer to provide definitive proof supporting BM pDC conversion into CD11b(+) cDC during in vivo viral infection. We show that in vivo BM pDC conversion into CD11b(+) cDC relates to enhanced ability to prime virus-specific T cells. Furthermore, we demonstrate that in vivo pDC conversion does not rely on viral infection of BM pDC, but instead is mediated by type I IFN signaling. Finally, by exploiting recently identified pDC-specific Ab, we provide further characterizations of the BM pDC fraction that exhibits this broader developmental plasticity. Collectively, these data indicate that BM pDC actively contribute to the CD11b(+) cDC pool during in vivo viral infection and delineates molecular, functional, and phenotypic features of this novel developmental pathway.
Liou
Li-Ying
LY
Viral-Immunobiology Laboratory, Department of Immunology and Microbial Science, IMM6, The Scripps Research Institute, La Jolla, CA, USA.
Blasius
Amanda L
AL
Welch
Megan J
MJ
Colonna
Marco
M
Oldstone
Michael B A
MB
Zuniga
Elina I
EI
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology*; D039481:CD11b Antigen / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL
D039481:CD11b Antigen; D007370:Interferon Type I