1. Altered immune response of immature dendritic cells following dengue virus infection in the presence of specific antibodies
- Author
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Silvia Torres, Vinit Upasani, Silvio Urcuqui-Inchima, Izabela A. Rodenhuis-Zybert, Heidi van der Ende-Metselaar, Jacky Flipse, Jolanda M. Smit, and Microbes in Health and Disease (MHD)
- Subjects
0301 basic medicine ,viruses ,Dengue virus ,medicine.disease_cause ,Antibodies, Viral ,Virus Replication ,DISEASE ,Dengue ,Interferon ,Aedes ,SEMI-MATURE ,Cricetinae ,Membrane Glycoproteins ,virus diseases ,hemic and immune systems ,Cytokines ,medicine.drug ,INTERFERON ,030106 microbiology ,Antigen presentation ,Immunoglobulins ,chemical and pharmacologic phenomena ,Biology ,Major histocompatibility complex ,MATURATION ,Cell Line ,03 medical and health sciences ,Immune system ,Antigen ,Immunity ,Antigens, CD ,Virology ,ANTIGEN PRESENTATION ,medicine ,Animals ,Humans ,COMPLEX ,Receptors, IgG ,CYTOKINE PRODUCTION ,Dendritic Cells ,HLA-DR Antigens ,biochemical phenomena, metabolism, and nutrition ,Dengue Virus ,Antibodies, Neutralizing ,HEMORRHAGIC-FEVER ,030104 developmental biology ,Viral replication ,FC-GAMMA-RIIA ,Immunology ,biology.protein ,B7-2 Antigen ,DEPENDENT ENHANCEMENT - Abstract
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 FcyRIla. Altogether, our data show that the presence of DENV-IC alters the phenotype and cytokine profile of DCs.
- Published
- 2016