Altered immune response of immature dendritic cells following dengue virus infection in the presence of specific antibodies.
Dengue virus (DENV) replication is known to prevent maturation of infected dendritic cells (DCs) thereby impeding the development of adequate immunity. During secondary DENV infection, dengue-specific antibodies can suppress DENV replication in immature DCs (immDCs), however how dengue-antibody complexes (DENV-IC) influence the phenotype of DCs remains elusive. Here, we evaluated the maturation state and cytokine profile of immDCs exposed to DENV-ICs. Indeed, DENV infection of immDCs in the absence of antibodies was hallmarked by blunted upregulation of CD83, CD86 and the major histocompatibility complex molecule HLA-DR. In contrast, DENV infection in the presence of neutralizing antibodies triggered full DC maturation and induced a balanced inflammatory cytokine response. Moreover, DENV infection under non-neutralizing conditions prompted upregulation of CD83 and CD86 but not HLA-DR, and triggered production of pro-inflammatory cytokines. The effect of DENV-IC was found to be dependent on the engagement of FcγRIIa. Altogether, our data show that the presence of DENV-IC alters the phenotype and cytokine profile of DCs.
Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.|Grupo Inmunovirologia, Facultad de Medicina, Universidad de Antioquia, UdeA calle 70 No. 52-21, Medellín, Colombia.
Silvia
S
Torres
Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Jacky
J
Flipse
Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Vinit C
VC
Upasani
Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Heidi
H
van der Ende-Metselaar
Grupo Inmunovirologia, Facultad de Medicina, Universidad de Antioquia, UdeA calle 70 No. 52-21, Medellín, Colombia.
Silvio
S
Urcuqui-Inchima
Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Jolanda M
JM
Smit
Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Izabela A
IA
Rodenhuis-Zybert
D000330:Aedes; D000818:Animals; D057134:Antibodies, Neutralizing / Q000235:genetics; D000914:Antibodies, Viral / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis; D051940:B7-2 Antigen / Q000096:biosynthesis; D002460:Cell Line; D006224:Cricetinae; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000821:virology*; D003715:Dengue / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000276:immunology*; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D017452:Receptors, IgG / Q000276:immunology; D014779:Virus Replication; D000097802:CD83 Antigen
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015703:Antigens, CD; D051940:B7-2 Antigen; D016207:Cytokines; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D017452:Receptors, IgG; D000097802:CD83 Antigen; C080568:Fc gamma receptor IIA