GSBS Student Publications

Title

Viral replication and paracrine effects result in distinct, functional responses of dendritic cells following infection with dengue 2 virus

UMMS Affiliation

Graduate School of Biomedical Sciences; Center for Infectious Disease and Vaccine Research

Date

7-26-2008

Document Type

Article

Medical Subject Headings

Chemokines; Cytokines; Dendritic Cells; Dengue; Dengue Virus; Disease Susceptibility; Flow Cytometry; Humans; Monocytes; T-Lymphocytes; Thymidine; Virus Replication

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Dengue virus (DENV), a re-emerging arbovirus, readily infects dendritic cells (DC) in culture and in vivo. However, there have been contradictory reports regarding the effect of DENV infection on DC activation and maturation. DC undergo a series of functional changes following exposure to infectious agents, including cytokine production and costimulatory and MHC molecule induction, culminating in stimulation of adaptive immune responses. Immunological memory to primary DENV infection critically influences disease severity during subsequent infections with heterologous serotypes. To explore these phenomena, we examined DENV infection-dependent and -independent effects on DC secretory, phenotypic, and allostimulatory functions. DENV infection of DC resulted in the secretion of a broad array of cytokines and chemokines. Type I IFN produced by DC inhibited propagation of infection and induced the chemokine IFN-gamma-inducible protein 10 (IP-10; CXCL10). Based on intracellular cytokine staining, infected DC produced less IP-10 but more TNF-alpha than uninfected bystander cells in the same culture. DENV exposure activated surface molecule expression on infected and bystander cells; infected DC had enhanced programmed death ligand 2 (PD-L2) and MHC II expression but reduced levels of PD-L1, CD80, CD86, and MHC I relative to bystander DC. Dengue-infected DC cultures stimulated resting allogeneic CD4 T cell proliferation, although an increasing multiplicity of infection was associated with decreasing stimulatory capacity of DC. These data demonstrate that functional maturation of DC in response to dengue infection is modified by the presence of virus through IFN-dependent and -independent mechanisms with consequences for the development of adaptive immunity.

Rights and Permissions

Citation: J Leukoc Biol. 2008 Oct;84(4):1028-38. Epub 2008 Jul 23. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal Title

Journal of leukocyte biology

PubMed ID

18653464