title: Brugia malayi infective larvae fail to activate Langerhans cells and dermal dendritic cells in human skin.
abstract: Filarial infection in humans is initiated when a mosquito deposits third-stage parasite larvae (L3) in the skin. Langerhans cells (LCs) and dermal dendritic cells (DDCs) are the first cells that the parasite encounters, and L3s must evade these highly effective antigen-presenting cells to establish infection. To assess LC and DDC responses to L3 in human skin, we employed three models of increasing physiologic relevance: in vitro-generated LCs, epidermal blister explants and full-thickness human skin sections. In vitro-generated LCs expressed TLR1-10 and robustly produced IL-6 and TNF-α in response to PolyI:C, but pre-exposure to L3s did not alter inflammatory cytokine production or TLR expression. L3s did not modulate expression of LC markers CDH1, CD207, or CD1a, or the regulatory products TSLP or IDO in epidermal explants or in vitro-generated LC. LC, CD14+ DDC, CD1c+ DC and CD141+ DC from human skin sections were analysed by flow cytometry. While PolyI:C potently induced CCL22 production in LC, CD1c+ DC, and CD141+ DC, and IL-10 production in LC, L3s did not modulate the numbers of or cytokine production by any skin DC subset. L3s broadly failed to activate or modulate LCs or DDCs, suggesting filarial larvae expertly evade APC detection in human skin.
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MA, USA.
authors.forename: R N
authors.initials: RN
authors.lastname: Cotton
authors.forename: R
authors.initials: R
authors.lastname: McDonald-Fleming
authors.forename: A
authors.initials: A
authors.lastname: Boyd
authors.forename: K
authors.initials: K
authors.lastname: Spates
authors.forename: T B
authors.initials: TB
authors.lastname: Nutman
authors.forename: R
authors.initials: R
authors.lastname: Tolouei Semnani
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D017178:Brugia malayi / Q000254:growth & development / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology; D007801:Langerhans Cells / Q000276:immunology*; D007814:Larva / Q000276:immunology; D012867:Skin / Q000166:cytology / Q000276:immunology* / Q000469:parasitology
chemical_list: D016207:Cytokines
keywords: Brugia malayi; dermal dendritic cells; langerhans cells