Hematopoietic and nonhematopoietic cells promote Type I interferon- and TLR7-dependent monocytosis during low-dose LCMV infection.
Release of inflammatory monocytes from the bone marrow (BM) into the blood is an important physiological response to infection, but the mechanisms regulating this phenomenon during viral infection are not completely defined. Here, we show that low-dose infection with lymphocytic choriomeningitis virus (LCMV) caused rapid, transient inflammatory monocytosis that required type I interferon (IFN) and Toll-like receptor (TLR) 7 signaling. Type I IFN and TLR7 signals were critical for induction of IFN-stimulated gene expression and CCR2 ligand upregulation in the BM microenvironment in response to LCMV infection. Experiments utilizing BM chimeric mice demonstrated that type I IFN and TLR7 signaling on either hematopoietic or nonhematopoietic cells was sufficient to initiate monocytosis in response to LCMV infection. BM plasmacytoid dendritic cells (pDCs) generated type I IFN directly ex vivo, suggesting that pDCs are a hematopoietic contributor of type I IFN in the BM early during LCMV infection. Overall, we describe novel roles for type I IFN and TLR7 signaling in nonhematopoietic cells and BM pDCs in directing IFN-stimulated gene and CCR2 ligand expression in the BM to initiate an increase in blood inflammatory monocytes during viral infection.
Department of Immunology, University of Washington, Seattle, WA, USA.|Immunology Research Program, Benaroya Research Institute (BRI) at Virginia Mason, Seattle, WA, USA.
Matthew B
MB
Buechler
Immunology Research Program, Benaroya Research Institute (BRI) at Virginia Mason, Seattle, WA, USA.
Griffin M
GM
Gessay
Department of Immunology, University of Washington, Seattle, WA, USA.|Immunology Research Program, Benaroya Research Institute (BRI) at Virginia Mason, Seattle, WA, USA.
Shivani
S
Srivastava
Department of Immunology, University of Washington, Seattle, WA, USA.|Immunology Research Program, Benaroya Research Institute (BRI) at Virginia Mason, Seattle, WA, USA.
Daniel J
DJ
Campbell
Department of Immunology, University of Washington, Seattle, WA, USA.|Immunology Research Program, Benaroya Research Institute (BRI) at Virginia Mason, Seattle, WA, USA.
Jessica A
JA
Hamerman
D000818:Animals; D001117:Arenaviridae Infections / Q000097:blood / Q000276:immunology*; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007370:Interferon Type I / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology*
D007370:Interferon Type I; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7
Lymphocytic choriomeningitis virus infection; Monocytes; Plasmacytoid DC; TLR7; Type I IFN