title: Subcapsular sinus macrophages limit dissemination of West Nile virus particles after inoculation but are not essential for the development of West Nile virus-specific T cell responses.
abstract: Macrophages encounter flaviviruses early after injection by arthropod vectors. Using in vivo imaging of mice inoculated with firefly luciferase-expressing single-cycle flavivirus particles (FLUC-SCFV), we examined the initial dissemination of virus particles in the presence or absence of lymph node (LN)-resident macrophages. Higher luciferase activity, indicating higher SCFV gene expression, was detected in the footpad of macrophage-depleted mice after 24h post infection (hpi). Moreover, FLUC-SCFV particles disseminated to the spleen within 14 hpi in macrophage-depleted, but not control mice. Although macrophages presented SCFV to naïve T cells in vitro, depletion of subcapsular sinus (SCS) macrophages did not alter the magnitude or effector function of the WNV-specific CD8(+) T cell response. Together, these results indicate that SCS macrophages play a role in limiting the dissemination of SCFV early in infection but are not required for the generation of a polyfunctional WNV-specific CD8(+) T cell response in the draining LN.
authors: Department of Pathology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA.
authors: Evandro R
authors: ER
authors: Winkelmann
authors: Department of Microbiology and Immunology, UTMB, Galveston, TX, USA.
authors: Douglas G
authors: DG
authors: Widman
authors: Department of Microbiology and Immunology, UTMB, Galveston, TX, USA.
authors: Jingya
authors: J
authors: Xia
authors: Department of Microbiology and Immunology, UTMB, Galveston, TX, USA.
authors: Alison J
authors: AJ
authors: Johnson
authors: Vrije Universiteit, Amsterdam, The Netherlands.
authors: Nico
authors: N
authors: van Rooijen
authors: Department of Pathology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA.
authors: Peter W
authors: PW
authors: Mason
authors: Department of Pediatrics, UTMB, 301 University Boulevard, Galveston, TX 77555-0436, USA; Sealy Center for Vaccine Development, UTMB, Galveston, TX 77555-0436, USA.
authors: Nigel
authors: N
authors: Bourne
authors: Department of Microbiology and Immunology, UTMB, Galveston, TX, USA; Department of Pediatrics, UTMB, 301 University Boulevard, Galveston, TX 77555-0436, USA; Sealy Center for Vaccine Development, UTMB, Galveston, TX 77555-0436, USA. Electronic address: gnmillig@utmb.edu.
authors: Gregg N
authors: GN
authors: Milligan
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018932:Chemokine CCL2 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D013154:Spleen / Q000276:immunology / Q000821:virology; D014901:West Nile Fever / Q000276:immunology* / Q000821:virology; D014902:West Nile virus / Q000235:genetics / Q000502:physiology*
chemical_list: D018932:Chemokine CCL2; D015850:Interleukin-6
keywords: CD8(+) T cell; RepliVAX; Single-cycle flavivirus; West Nile virus; subcapsular sinus macrophages