@article{fdi:010074360,
  title = {{I}nnate immune response of primary human keratinocytes to {W}est {N}ile {V}irus {I}nfection and its modulation by mosquito saliva},
  author = {{G}arcia, {M}. and {A}lout, {H}. and {D}iop, {F}od{\'e} and {D}amour, {A}. and {B}engue, {M}. and {W}eill, {M}. and {M}iss{\'e}, {D}oroth{\'e}e and {L}{\'e}v{\^e}que, {N}. and {B}odet, {C}.},
  editor = {},
  language = {{ENG}},
  abstract = {{W}est {N}ile {V}irus ({WNV}) is a flavivirus involved in many human infections worldwide. {T}his arthropod-borne virus is directly co-inoculated with mosquito saliva through the epidermis and the dermis during blood meal. {WNV} starts replicating in the skin before migrating to the draining lymph node, leading to widespread viremia and in some cases to neurological symptoms. {S}kin is a complex organ composed of different cell types that together perform essential functions such as pathogen sensing, barrier maintenance and immunity. {K}eratinocytes, which represent 90% of the cells of the epidermis, are the organism's first line of defense, initiating innate immune response by recognizing pathogens through their pattern recognition receptors. {A}lthough {WNV} was previously known to replicate in human primary keratinocytes, the induced inflammatory response remains unknown. {T}he aim of this study was first to characterize the inflammatory response of human primary keratinocytes to {WNV} infection and then, to assess the potential role of co-inoculated mosquito saliva on the keratinocyte immune response and viral replication. {A} type {I} and {III} interferon inflammatory response associated with an increase of {IRF}7 but not {IRF}3 m{RNA} expression, and dependent on infectious dose, was observed during keratinocyte infection with {WNV}. {E}xpression of several interferon-stimulated gene m{RNA} was also increased at 24 h post-infection (p.i.); they included {CXCL}10 and interferon-induced proteins with tetratricopeptide repeats ({IFIT})-2 sustained up until 48 h p.i. {M}oreover, {WNV} infection of keratinocyte resulted in a significant increase of pro-inflammatory cytokines ({TNF} alpha, {IL}-6) and various chemokines ({CXCL}1, {CXCL}2, {CXCL}8 and {CCL}20) expression. {T}he addition of {A}edes aegypti or {C}ulex quinquefasciatus mosquito saliva, two vectors of {WNV} infection, to infected keratinocytes led to a decrease of inflammatory response at 24 h p.i. {H}owever, only {A}e. {A}egypti saliva adjunction induced modulation of viral replication. {I}n conclusion, this work describes for the first time the inflammatory response of human primary keratinocytes to {WNV} infection and its modulation in presence of vector mosquito saliva. {T}he effects of mosquito saliva assessed in this work could be involved in the early steps of {WNV} replication in skin promoting viral spread through the body.},
  keywords = {{W}est {N}ile virus ; keratinocytes ; mosquito ; saliva ; immunomodulation ; innate immune response ; viral replication ; interferon-stimulated genes},
  booktitle = {},
  journal = {{F}rontiers in {C}ellular and {I}nfection {M}icrobiology},
  volume = {8},
  numero = {},
  pages = {art. 387 [13 p.]},
  ISSN = {2235-2988},
  year = {2018},
  DOI = {10.3389/fcimb.2018.00387},
  URL = {https://www.documentation.ird.fr/hor/fdi:010074360},
}