title: Rapid differentiation of monocytes into type I IFN-producing myeloid dendritic cells as an antiviral strategy against influenza virus infection.
abstract: Myeloid dendritic cells (mDCs) have long been thought to function as classical APCs for T cell responses. However, we demonstrate that influenza viruses induce rapid differentiation of human monocytes into mDCs. Unlike the classic mDCs, the virus-induced mDCs failed to upregulate DC maturation markers and were unable to induce allogeneic lymphoproliferation. Virus-induced mDCs secreted little, if any, proinflammatory cytokines; however, they secreted a substantial amount of chemoattractants for monocytes (MCP-1 and IP-10). Interestingly, the differentiated mDCs secreted type I IFN and upregulated the expression of IFN-stimulated genes (tetherin, IFITM3, and viperin), as well as cytosolic viral RNA sensors (RIG-I and MDA5). Additionally, culture supernatants from virus-induced mDCs suppressed the replication of virus in vitro. Furthermore, depletion of monocytes in a mouse model of influenza infection caused significant reduction of lung mDC numbers, as well as type I IFN production in the lung. Consequently, increased lung virus titer and higher mortality were observed. Taken together, our results demonstrate that the host responds to influenza virus infection by initiating rapid differentiation of circulating monocytes into IFN-producing mDCs, which contribute to innate antiviral immune responses.
authors.affiliation: Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Weiping
authors.initials: W
authors.lastname: Cao
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Taylor
authors.forename: Renata E
authors.initials: RE
authors.lastname: Biber
authors.forename: William G
authors.initials: WG
authors.lastname: Davis
authors.forename: Jin Hyang
authors.initials: JH
authors.lastname: Kim
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Reber
authors.forename: Tatiana
authors.initials: T
authors.lastname: Chirkova
authors.forename: Juan A
authors.initials: JA
authors.lastname: De La Cruz
authors.forename: Aseem
authors.initials: A
authors.lastname: Pandey
authors.forename: Priya
authors.initials: P
authors.lastname: Ranjan
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Katz
authors.forename: Shivaprakash
authors.initials: S
authors.lastname: Gangappa
authors.forename: Suryaprakash
authors.initials: S
authors.lastname: Sambhara
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D007370:Interferon Type I / Q000096:biosynthesis* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D007370:Interferon Type I