Interleukin-1beta 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 migrate out of the epidermis into the lymphatics and travel to the draining lymph nodes where they are responsible for the activation of T cells in the primary immune response. Tumor necrosis factor and interleukin-1beta, have previously been shown to be responsible for Langerhans cell migration in response to contact sensitizers in BALB/C mice; however, which cytokines are responsible for mediating Langerhans cell migration in response to a replicating cutaneously acquired virus such as the West Nile Virus, are not known. We have devised a method for identifying Langerhans cells in the draining lymph nodes using E-cadherin labeling and flow cytometry. We infected tumor necrosis factor-deficient gene knockout mice (tumor necrosis factor-/-) intradermally with West Nile Virus and found that levels of Langerhans cell 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 inhibit the migration of Langerhans cells from the epidermis and their accumulation in the draining lymph nodes in wild-type C57BL/6 mice. In West Nile Virus-infected, tumor necrosis factor-/- mice treated with systemic neutralizing anti-interleukin-1beta 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, infected animals. The results indicate that Langerhans cell migration, accumulation 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 interleukin-1beta and can occur in the absence of tumor necrosis factor.
Byrne
S N
SN
Department of Pathology, University of Sydney, Sydney, New South Wales, Australia.
Halliday
G M
GM
Johnston
L J
LJ
King
N J
NJ
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D007375:Interleukin-1 / Q000276:immunology* / Q000494:pharmacology; D007801:Langerhans Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D012867:Skin / Q000276:immunology* / Q000473:pathology / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D014901:West Nile Fever / Q000276:immunology* / Q000473:pathology; D014902:West Nile virus
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha