Abstract
Following repeat exposure to many human adenoviruses (HAdVs), most adults harbour long-lived B- and T-cell responses. Combined, this response typically protects us for years from re-infection by the same HAdV type. In spite of these immune responses, some HAdV types are associated with persistent infections that constitute a life-threatening risk when an individual’s T-cell response is compromised. By contrast, patients with B-cell deficiencies do not appear to be at a greater risk of HAdV disease. This dichotomy begs the question of the secondary role of anti-HAdV antibodies during host defence. In this study, we explored IgG-complexed (IC)-HAdV5 and primary human plasmacytoid dendritic cell (pDC) interactions. We found that IC-HAdV5 are efficiently internalized in pDCs, stimulate their activation through TLR9 signalling, and cause apoptosis. These data may help reconcile the enigma of robust immune response to HAdVs, while concurrently allowing persistence.
Highlights
Plasmacytoid dendritic cells are a subset of phagocytes continuously produced in the bone marrow and, via the peripheral blood, are recruited to breaches in tissue homeostasis [1]
Human adenoviruses (HAdVs) belong to the genus Mastadenoviridae and are grouped into seven species (A–G), which include approximately 100 types that are grouped by serology and/or sequence phylogeny [4]
We argue that understanding the divergent roles of plasmacytoid dendritic cell (pDC) in antiviral immunity vs. tolerance will help resolve the discord between the robust immune response to HAdV and the ability to induce latent infections [7,8]
Summary
Plasmacytoid dendritic cells (pDCs) are a subset of phagocytes continuously produced in the bone marrow and, via the peripheral blood, are recruited to breaches in tissue homeostasis [1]. During a response to viral infections, the hallmark of pDCs is their ability to secrete relatively high levels of type 1 interferons (IFN-1). Combined with the innate immune responses from infected cells and other recruited immune cells, the cytokine profile of pDCs biases the adaptive immune response toward an antiviral Th1 response [2]. They are found on every continent and include more than 300 types isolated from mammals, fish, birds, and reptiles. Human adenoviruses (HAdVs) belong to the genus Mastadenoviridae and are grouped into seven species (A–G), which include approximately 100 types that are grouped by serology and/or sequence phylogeny [4]
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