@article{fdi:010086501,
  title = {{E}valuation of cutaneous immune response in a controlled human in vivo model of mosquito bites},
  author = {{G}uerrero, {D}. and {V}o, {H}. {T}. {M}. and {L}on, {C}. and {B}ohl, {J}. {A}. and {N}hik, {S}. and {C}hea, {S}. and {M}an, {S}. and {S}reng, {S}. and {P}acheco, {A}. {R}. and {L}y, {S}. and {S}ath, {R}. and {L}ay, {S}. and {M}iss{\'e}, {D}oroth{\'e}e and {H}uy, {R}. and {L}eang, {R}. and {K}ry, {H}. and {V}alenzuela, {J}. {G}. and {O}liveira, {F}. and {C}antaert, {T}. and {M}anning, {J}. {E}.},
  editor = {},
  language = {{ENG}},
  abstract = {{M}osquito-borne viruses are a growing global threat. {I}nitial viral inoculation occurs in the skin via the mosquito 'bite', eliciting immune responses that shape the establishment of infection and pathogenesis. {H}ere we assess the cutaneous innate and adaptive immune responses to controlled {A}edes aegypti feedings in humans living in {A}edes-endemic areas. {I}n this single-arm, cross-sectional interventional study (trial registration #{NCT}04350905), we enroll 30 healthy adult participants aged 18 to 45 years of age from {C}ambodia between {O}ctober 2020 and {J}anuary 2021. {W}e perform 3-mm skin biopsies at baseline as well as 30 min, 4 h, and 48 h after a controlled feeding by uninfected {A}edes aegypti mosquitos. {T}he primary endpoints are measurement of changes in early and late innate responses in bitten vs unbitten skin by gene expression profiling, immunophenotyping, and cytokine profiling. {T}he results reveal induction of neutrophil degranulation and recruitment of skin-resident dendritic cells and {M}2 macrophages. {A}s the immune reaction progresses {T} cell priming and regulatory pathways are upregulated along with a shift to {T}(h)2-driven responses and {CD}8(+) {T} cell activation. {S}timulation of participants' bitten skin cells with {A}edes aegypti salivary gland extract results in reduced pro-inflammatory cytokine production. {T}hese results identify key immune genes, cell types, and pathways in the human response to mosquito bites and can be leveraged to inform and develop novel therapeutics and vector-targeted vaccine candidates to interfere with vector-mediated disease. {V}ector-borne pathogens are known to elicit immune response upon mosquito biting the host which is critically linked to the establishment of infection and pathogenesis of disease, yet the impact of the mosquito bite itself is not immunologically well-appreciated. {H}ere the authors characterize the immune response to the mosquito vector {A}edes aegypti in a controlled human in vivo challenge model and show the induction of a range of immune pathways and cell types.},
  keywords = {{CAMBODGE}},
  booktitle = {},
  journal = {{N}ature {C}ommunications},
  volume = {13},
  numero = {1},
  pages = {7036 [13 p.]},
  year = {2022},
  DOI = {10.1038/s41467-022-34534-9},
  URL = {https://www.documentation.ird.fr/hor/fdi:010086501},
}