Cutaneous RANK-RANKL Signaling Upregulates CD8-Mediated Antiviral Immunity during Herpes simplex Virus Infection by Preventing Virus-Induced Langerhans Cell Apoptosis
| Autor: | Joachim E. Kühn, Björn E. Clausen, Eva Lorentzen, Wali Hafezi, Lars Klenner, Thomas A. Luger, Stefan Beissert, Karin Loser |
|---|---|
| Přispěvatelé: | Immunology |
| Rok vydání: | 2015 |
| Předmět: |
Langerhans cell
CD8 Antigens viruses Priming (immunology) Apoptosis Mice Transgenic chemical and pharmacologic phenomena Herpesvirus 1 Human Dermatology CD8-Positive T-Lymphocytes Biology Sensitivity and Specificity Biochemistry Virus Mice Random Allocation Immune system Antigen Immunity medicine Animals Humans Cytotoxic T cell Molecular Biology Cells Cultured Receptor Activator of Nuclear Factor-kappa B RANK Ligand Herpes Simplex hemic and immune systems Cell Biology Up-Regulation Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Langerhans Cells Immunology Biomarkers CD8 Signal Transduction |
| Zdroj: | Journal of Investigative Dermatology, 135(11), 2676-2687. Nature Publishing Group Europe PubMed Central |
| ISSN: | 0022-202X |
| DOI: | 10.1038/jid.2015.225 |
| Popis: | Herpes simplex virus-type 1 (HSV-1) causes the majority of cutaneous viral infections. Viral infections are controlled by the immune system, and CD8(+) cytotoxic T-lymphocytes (CTLs) have been shown to be crucial during the clearance of HSV-1 infections. Although epidermal Langerhans cells (LCs) are the first dendritic cells (DCs) to come into contact with the virus, it has been shown that the processing of viral antigens and the differentiation of antiviral CTLs are mediated by migratory CD103+ dermal DCs and CD8 alpha(+) lymph node resident DCs. In vivo regulatory T-cells (Tregs) are implicated in the regulation of antiviral immunity and we have shown that signaling via the receptor activator of NF-0 (RANK) and its ligand RANKL mediates the peripheral expansion of Tregs. However, in addition to expanding Tregs, RANK RANKL interactions are involved in the control of antimicrobial immunity by upregulating the priming of CD4(+) effector T cells in LCMV infection or by the generation of parasite-specific CD8(+) T cells in Trypanosoma cruzi infection. Here, we demonstrate that cutaneous RANK RANKL signaling is critical for the induction of CD8-mediated antiviral immune responses during HSV-1 infection of the skin by preventing virus-induced LC apoptosis, improving antigen transport to regional lymph nodes, and increasing the CTL priming capacity of lymph node DCs. |
| Databáze: | OpenAIRE |
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