Interleukin-1 beta but not tumor necrosis factor is involved in West Nile Virus-induced Langerhans cell migration from the skin in C57BL/6 mice

Langerhans cells are bone marrow-derived epidermal dendritic cells. They mi grate out of the epidermis into the lymphatics and travel to the draining l ymph nodes where they are responsible for the activation of T cells in the primary immune response. Tumor necrosis factor and interleukin-1 beta, have previously been shown to be responsible for Langerhans cell migration in r esponse to contact sensitizers in BALB/C mice; however, which cytokines are responsible for mediating Langerhans cell migration in response to a repli cating cutaneously acquired virus such as the West Nile Virus, are not know n. We have devised a method for identifying Langerhans cells in the drainin g lymph nodes using E-cadherin labeling and flow cytometry. We infected tum or necrosis factor-deficient gene knockout mice (tumor necrosis factor(-/-) ) intradermally with West Nile Virus and found that levels of Langerhans ce ll emigration and accumulation in the draining lymph nodes were similar to wild-type C57BL/6 mice. This was borne out by the finding that high levels of systemic neutralizing anti-tumor necrosis factor antibody failed to inhi bit the migration of Langerhans cells from the epidermis and their accumula tion in the draining lymph nodes in wild-type C57BL/6 mice. In West Nile Vi rus-infected, tumor necrosis factor(-/-) mice treated with systemic neutral izing anti-interleuldn-1 beta antibodies, however, migration of Langerhans cells from the epidermis and their accumulation in the draining lymph nodes were significantly inhibited compared with control antibody-treated, infec ted animals. The results indicate that Langerhans cell migration, accumulat ion in the draining lymph nodes and the initiation of lymph node shut-down in response to a cutaneous West Nile Virus infection is dependent on interl eukin-1 beta and can occur in the absence of tumor necrosis factor.