title: Filaria-induced immune evasion: suppression by the infective stage of Brugia malayi at the earliest host-parasite interface.
abstract: To assess the physiologic interactions between the infective stage of Brugia malayi--one of the extracellular parasites responsible for lymphatic filariasis in humans--and the APC with which they come in contact during their development and routes of travel, we have investigated the interaction between the infective stage (L3) of B. malayi and human Langerhans cells (LC) in the skin. Our data indicate that live L3 result in increased migration of LC from the epidermis without affecting the viability of these cells and up-regulation of the IL-18 cytokine involved in LC migration. Live L3 also result in down-regulation of MHC class I and II on the LC cell surface. Additionally, microarray data indicate that live L3 significantly down-regulated expression of IL-8 as well as of multiple genes involved in Ag presentation, reducing the capacity of LC to induce CD4(+) T cells in allogeneic MLR, and thus resulting in a decreased ability of LC to promote CD4(+) T cell proliferation and production of IFN-gamma and IL-10. These data suggest that L3 exert a down-regulatory response in epidermal LC that leads to a diminished capacity of these cells to activate CD4(+) T cells.
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. rsemnani@niaid.nih.gov
authors.forename: Roshanak Tolouei
authors.initials: RT
authors.lastname: Semnani
authors.forename: Melissa
authors.initials: M
authors.lastname: Law
authors.forename: Joseph
authors.initials: J
authors.lastname: Kubofcik
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D000947:Antigens, Helminth / Q000378:metabolism; D017178:Brugia malayi / Q000254:growth & development* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D046508:Culture Techniques; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000276:immunology; D004817:Epidermis / Q000276:immunology / Q000469:parasitology; D005786:Gene Expression Regulation / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D020382:Interleukin-18 / Q000096:biosynthesis; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D012867:Skin / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000947:Antigens, Helminth; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D020382:Interleukin-18