Premium
Brugia malayi infective larvae fail to activate Langerhans cells and dermal dendritic cells in human skin
Author(s) -
Cotton R. N.,
McDonaldFleming R.,
Boyd A.,
Spates K.,
Nutman T. B.,
Tolouei Semnani R.
Publication year - 2015
Publication title -
parasite immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 75
eISSN - 1365-3024
pISSN - 0141-9838
DOI - 10.1111/pim.12169
Subject(s) - biology , human skin , immunology , brugia malayi , cytokine , in vitro , langerhans cell , interleukin 10 , flow cytometry , dendritic cell , proinflammatory cytokine , immune system , inflammation , filariasis , helminths , biochemistry , genetics
Summary Filarial infection in humans is initiated when a mosquito deposits third‐stage parasite larvae (L3) in the skin. Langerhans cells ( LC s) and dermal dendritic cells ( DDC s) 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 LC s, epidermal blister explants and full‐thickness human skin sections. In vitro‐generated LC s expressed TLR 1‐10 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 CDH 1, CD 207, or CD 1a, or the regulatory products TSLP or IDO in epidermal explants or in vitro ‐generated LC . LC , CD 14+ DDC , CD 1c+ DC and CD 141+ DC from human skin sections were analysed by flow cytometry. While PolyI:C potently induced CCL 22 production in LC , CD 1c+ DC , and CD 141+ 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 LC s or DDC s, suggesting filarial larvae expertly evade APC detection in human skin.