Cutaneous RANK-RANKL Signaling Upregulates CD8-Mediated Antiviral Immunity during Herpes simplex Virus Infection by Preventing Virus-Induced Langerhans Cell Apoptosis.
J Invest Dermatol
; 135(11): 2676-2687, 2015 Nov.
Article
em En
| MEDLINE
| ID: mdl-26076314
ABSTRACT
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 CD8α(+) 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-κB (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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
/
4_TD
/
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Células de Langerhans
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Linfócitos T CD8-Positivos
/
Ligante RANK
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Receptor Ativador de Fator Nuclear kappa-B
/
Herpes Simples
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Invest Dermatol
Ano de publicação:
2015
Tipo de documento:
Article