Langerhans Cells Migrate to Local Lymph Nodes Following Cutaneous Infection with an Arbovirus

Abstract

Whereas there has been recent interest in interactions between dendritic cells and pathogenic viruses, the role of dendritic cells in the initiation of protective immunity to such organisms has not been elucidated. The aim of this study was to examine whether a resident dendritic cell population in the skin, Langerhans cells, respond to cutaneous viral infections which are effectively cleared by the immune system. We therefore characterized the ability of Langerhans cells to migrate to local draining lymph nodes following infection with the arthropod-borne viruses, West Nile virus or Semliki Forest virus. The data show that major histocompatibility complex class II+/NLDC145+/E-cadherin+ Langerhans cell numbers are increased in the draining lymph nodes of infected mice and this increase is accompanied by a concomitant decrease in the Langerhans cell density in the epidermis. Langerhans cell migration is associated with an accumulation of leukocytes in the lymph node, which is one of the earliest events in the initiation of an immune response. Both the migratory response and the draining lymph node leukocyte accumulation were abrogated if ultraviolet-inactivated instead of live viruses were used, suggesting the activation and subsequent migration of Langerhans cells requires a live, replicating antigen. Our findings are likely to have wider implications for the development of epidermally delivered vaccines and suggest that mobilization of dendritic cells may be involved in the development of immune responses to arthropod-borne viruses.

Recombinant Semliki Forest virus vaccine vectors: the route of injection determines the localization of vector RNA and subsequent T cell response

“…A likely mechanism for the co-localized expression of antigen and T cell induction is that infected cells or possibly material from infected cells migrate to draining lymph nodes following s.c. injection. Langerhans cell migration to local lymph nodes following subcutaneous administration of replicative SFV has been shown previously 25 and it was associated with an accumulation of leukocytes in the LN. It was further Gene Therapy shown that recombinant VEE (another alphavirus) initially infected Langerhans cells in the skin, which migrated to draining lymph nodes upon subcutaneous inoculation.…”

Active Infection of Human Blood Monocytes by Chikungunya Virus Triggers an Innate Immune Response

“…Because monocytes postinfection do not produce high levels of infectious virus, this suggests that CHIKV may be produced in another compartment. It has been shown for some alphaviruses that early viral production may take place in the lymph nodes (19). More recently, P. Roques and collaborators (27) detected CHIKV replication in the lymph nodes of macaques in the first 2-3 d postinfection.…”

“…From there, the virus will find its way into the blood vessels before dissemination to the target tissues/or organs (17). Although the exact route and mechanisms of early infection is poorly defined (18), previous studies from other alphaviruses have indicated the involvement of different immune cell populations in the skin (19)(20)(21)(22), and migrating cells such as macrophages and/or dendritic cells (DCs) (19). The events taking place during the acute blood phase of CHIKV infections have not been clearly defined.…”

Viral envelope protein glycosylation is a molecular determinant of the neuroinvasiveness of the New York strain of West Nile virus

“…However, additional factors involved in the pathogenesis of WN viruses remain to be elucidated. It has been reported that the initial target of infection for dengue virus, a mosquito-borne flavivirus, are dendritic cells (Wu et al, 2000) and that dendritic cells migrate to the local lymph nodes following arbovirus infection (Johnston et al, 2000). However, subsequent events leading to viral invasion of the CNS remain unclear.…”