title: Differential cytokine responses from primary human Kupffer cells following infection with wild-type or vaccine strain yellow fever virus.
abstract: Wild-type yellow fever virus (YFV) infections result in a hepatotropic disease which is often fatal, while vaccination with the live-attenuated 17-D strain results in productive infection yet is well-tolerated with few adverse events. Kupffer cells (KCs) are resident liver macrophages that have a significant role in pathogen detection, clearance and immune signaling. Although KCs appear to be an important component of YF disease, their role has been under-studied. This study examined cytokine responses in KCs following infection with either wild-type or vaccine strains of YFV. Results indicate that KCs support replication of both wild-type and vaccine strains, yet wild-type YFV induced a prominent and prolonged pro-inflammatory cytokine response (IL-8, TNF-α and RANTES/CCL5) with little control by a major anti-inflammatory cytokine (IL-10). This response was significantly reduced in vaccine strain infections. These data suggest that a differentially regulated infection in KCs may play a critical role in development of disease.
authors.affiliation: Department of Pathology and Institute for Human Infection and Immunity, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77550, USA.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Woodson
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Freiberg
authors.forename: Michael R
authors.initials: MR
authors.lastname: Holbrook
mesh_terms: D000293:Adolescent; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D007728:Kupffer Cells / Q000276:immunology* / Q000821:virology*; D008297:Male; D015005:Yellow fever virus / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D016207:Cytokines