HMGB1, an alarmin promoting HIV dissemination and latency in dendritic cells.
Dendritic cells (DCs) initiate immune responses by transporting antigens and migrating to lymphoid tissues to initiate T-cell responses. DCs are located in the mucosal surfaces that are involved in human immunodeficiency virus (HIV) transmission and they are probably among the earliest targets of HIV-1 infection. DCs have an important role in viral transmission and dissemination, and HIV-1 has evolved different strategies to evade DC antiviral activity. High mobility group box 1 (HMGB1) is a DNA-binding nuclear protein that can act as an alarmin, a danger signal to alert the innate immune system for the initiation of host defense. It is the prototypic damage-associated molecular pattern molecule, and it can be secreted by innate cells, including DCs and natural killer (NK) cells. The fate of DCs is dependent on a cognate interaction with NK cells, which involves HMGB1 expressed at NK-DC synapse. HMGB1 is essential for DC maturation, migration to lymphoid tissues and functional type-1 polarization of naïve T cells. This review highlights the latest advances in our understanding of the impact of HIV on the interactions between HMGB1 and DCs, focusing on the mechanisms of HMGB1-dependent viral dissemination and persistence in DCs, and discussing the consequences on antiviral innate immunity, immune activation and HIV pathogenesis.
Antiviral Immunity, Biotherapy and Vaccine Unit, Infection and Epidemiology Department, Institut Pasteur, Paris, France. marie-lise.gougeon@pasteur.fr
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Gougeon
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Melki
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Saïdi
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology / Q000821:virology; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology / Q000821:virology; D016328:NF-kappa B / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000821:virology; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D017735:Virus Latency; D014779:Virus Replication
D024243:HMGB1 Protein; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4