title: Depletion of macrophages in mice results in higher dengue virus titers and highlights the role of macrophages for virus control.
abstract: Monocytes and macrophages are target cells for dengue infection. Besides their potential role for virus replication, activated monocytes/macrophages produce cytokines that may be critical for dengue pathology. To study the in vivo role of monocytes and macrophages for virus replication, we depleted monocytes and macrophages in IFN-alphabetagammaR knockout mice with clodronate liposomes before dengue infection. Although less virus was first recovered in the draining LN in the absence of macrophages, monocyte/macrophage depletion eventually resulted in a ten-fold higher systemic viral titer. A massive infiltration of CD11b(+)CD11c(low)Ly6C(low) monocytes into infected organs was observed in parallel with increasing virus titers before viremia was controlled. Depletion of monocytes in the blood before or after local infection had no impact on virus titers, suggesting that monocytes are not required as "virus-shuttles". Our data provide evidence that systemic viremia is established independently of tissue macrophages present at the site of infection and blood monocytes. Instead, we demonstrate the importance of monocytes/macrophages for the control of dengue virus.
authors.affiliation: Novartis Institute for Tropical Diseases, Biopolis, Singapore. Katja_Fink@immunol.a-star.edu.sg
authors.forename: Katja
authors.initials: K
authors.lastname: Fink
authors.forename: Cedrig
authors.initials: C
authors.lastname: Ng
authors.forename: Celine
authors.initials: C
authors.lastname: Nkenfou
authors.forename: Subhash G
authors.initials: SG
authors.lastname: Vasudevan
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Wouter
authors.initials: W
authors.lastname: Schul
mesh_terms: D000818:Animals; D002452:Cell Count; D002465:Cell Movement / Q000276:immunology; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology; D003715:Dengue / Q000276:immunology* / Q000821:virology*; D003716:Dengue Virus / Q000254:growth & development*; D000078404:Epidermal Cells; D004817:Epidermis / Q000821:virology; D006098:Granulocytes / Q000166:cytology; D007801:Langerhans Cells / Q000821:virology; D008081:Liposomes; D008196:Lymph / Q000821:virology; D008198:Lymph Nodes / Q000166:cytology / Q000821:virology; D008221:Lymphoid Tissue / Q000166:cytology / Q000821:virology; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000821:virology; D010537:Peritoneum / Q000166:cytology; D053633:Receptor, Interferon alpha-beta / Q000235:genetics; D017471:Receptors, Interferon / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000821:virology; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014766:Viremia; D000096743:Interferon gamma Receptor
chemical_list: D004002:Clodronic Acid; D008081:Liposomes; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon; D017361:Viral Nonstructural Proteins; D000096743:Interferon gamma Receptor; C079340:NS1 protein, Dengue virus type 2