Depletion of macrophages in mice results in higher dengue virus titers and highlights the role of macrophages for virus control.
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.
Fink
Katja
K
Novartis Institute for Tropical Diseases, Biopolis, Singapore. Katja_Fink@immunol.a-star.edu.sg
Ng
Cedrig
C
Nkenfou
Celine
C
Vasudevan
Subhash G
SG
van Rooijen
Nico
N
Schul
Wouter
W
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
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