Innate Immune Response of Primary Human Keratinocytes to West Nile Virus Infection and Its Modulation by Mosquito Saliva
West Nile Virus (WNV) is a flavivirus involved in many human infections worldwide. This 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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcimb.2018.00387/full |
| _version_ | 1811233845677129728 |
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| author | Magali Garcia Magali Garcia Haoues Alout Fodé Diop Alexia Damour Michèle Bengue Mylène Weill Dorothée Missé Nicolas Lévêque Nicolas Lévêque Charles Bodet |
| author_facet | Magali Garcia Magali Garcia Haoues Alout Fodé Diop Alexia Damour Michèle Bengue Mylène Weill Dorothée Missé Nicolas Lévêque Nicolas Lévêque Charles Bodet |
| author_sort | Magali Garcia |
| collection | DOAJ |
| description | West Nile Virus (WNV) is a flavivirus involved in many human infections worldwide. This 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. Skin is a complex organ composed of different cell types that together perform essential functions such as pathogen sensing, barrier maintenance and immunity. Keratinocytes, 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. Although WNV was previously known to replicate in human primary keratinocytes, the induced inflammatory response remains unknown. The 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 IRF7 but not IRF3 mRNA expression, and dependent on infectious dose, was observed during keratinocyte infection with WNV. Expression of several interferon-stimulated gene mRNA was also increased at 24 h post-infection (p.i.); they included CXCL10 and interferon-induced proteins with tetratricopeptide repeats (IFIT)-2 sustained up until 48 h p.i. Moreover, WNV infection of keratinocyte resulted in a significant increase of pro-inflammatory cytokines (TNFα, IL-6) and various chemokines (CXCL1, CXCL2, CXCL8 and CCL20) expression. The addition of Aedes aegypti or Culex quinquefasciatus mosquito saliva, two vectors of WNV infection, to infected keratinocytes led to a decrease of inflammatory response at 24 h p.i. However, only Ae. Aegypti saliva adjunction induced modulation of viral replication. In 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. The 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. |
| first_indexed | 2024-04-12T11:26:08Z |
| format | Article |
| id | doaj.art-1818fe6627734c33a19007d0b7bfd181 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-12T11:26:08Z |
| publishDate | 2018-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-1818fe6627734c33a19007d0b7bfd1812022-12-22T03:35:13ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882018-11-01810.3389/fcimb.2018.00387420232Innate Immune Response of Primary Human Keratinocytes to West Nile Virus Infection and Its Modulation by Mosquito SalivaMagali Garcia0Magali Garcia1Haoues Alout2Fodé Diop3Alexia Damour4Michèle Bengue5Mylène Weill6Dorothée Missé7Nicolas Lévêque8Nicolas Lévêque9Charles Bodet10Laboratoire de Virologie et Mycobactériologie, CHU de Poitiers, Poitiers, FranceLaboratoire Inflammation, Tissus Epithéliaux et Cytokines, EA 4331, Université de Poitiers, Poitiers, FranceInstitut des Sciences de l'Evolution, Université de Montpellier, Montpellier, FranceMIVEGEC UMR 224, Université de Montpellier, IRD, CNRS, Montpellier, FranceLaboratoire Inflammation, Tissus Epithéliaux et Cytokines, EA 4331, Université de Poitiers, Poitiers, FranceMIVEGEC UMR 224, Université de Montpellier, IRD, CNRS, Montpellier, FranceInstitut des Sciences de l'Evolution, Université de Montpellier, Montpellier, FranceMIVEGEC UMR 224, Université de Montpellier, IRD, CNRS, Montpellier, FranceLaboratoire de Virologie et Mycobactériologie, CHU de Poitiers, Poitiers, FranceLaboratoire Inflammation, Tissus Epithéliaux et Cytokines, EA 4331, Université de Poitiers, Poitiers, FranceLaboratoire Inflammation, Tissus Epithéliaux et Cytokines, EA 4331, Université de Poitiers, Poitiers, FranceWest Nile Virus (WNV) is a flavivirus involved in many human infections worldwide. This 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. Skin is a complex organ composed of different cell types that together perform essential functions such as pathogen sensing, barrier maintenance and immunity. Keratinocytes, 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. Although WNV was previously known to replicate in human primary keratinocytes, the induced inflammatory response remains unknown. The 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 IRF7 but not IRF3 mRNA expression, and dependent on infectious dose, was observed during keratinocyte infection with WNV. Expression of several interferon-stimulated gene mRNA was also increased at 24 h post-infection (p.i.); they included CXCL10 and interferon-induced proteins with tetratricopeptide repeats (IFIT)-2 sustained up until 48 h p.i. Moreover, WNV infection of keratinocyte resulted in a significant increase of pro-inflammatory cytokines (TNFα, IL-6) and various chemokines (CXCL1, CXCL2, CXCL8 and CCL20) expression. The addition of Aedes aegypti or Culex quinquefasciatus mosquito saliva, two vectors of WNV infection, to infected keratinocytes led to a decrease of inflammatory response at 24 h p.i. However, only Ae. Aegypti saliva adjunction induced modulation of viral replication. In 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. The 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.https://www.frontiersin.org/article/10.3389/fcimb.2018.00387/fullWest Nile viruskeratinocytesmosquitosalivaimmunomodulationinnate immune response |
| spellingShingle | Magali Garcia Magali Garcia Haoues Alout Fodé Diop Alexia Damour Michèle Bengue Mylène Weill Dorothée Missé Nicolas Lévêque Nicolas Lévêque Charles Bodet Innate Immune Response of Primary Human Keratinocytes to West Nile Virus Infection and Its Modulation by Mosquito Saliva Frontiers in Cellular and Infection Microbiology West Nile virus keratinocytes mosquito saliva immunomodulation innate immune response |
| title | Innate Immune Response of Primary Human Keratinocytes to West Nile Virus Infection and Its Modulation by Mosquito Saliva |
| title_full | Innate Immune Response of Primary Human Keratinocytes to West Nile Virus Infection and Its Modulation by Mosquito Saliva |
| title_fullStr | Innate Immune Response of Primary Human Keratinocytes to West Nile Virus Infection and Its Modulation by Mosquito Saliva |
| title_full_unstemmed | Innate Immune Response of Primary Human Keratinocytes to West Nile Virus Infection and Its Modulation by Mosquito Saliva |
| title_short | Innate Immune Response of Primary Human Keratinocytes to West Nile Virus Infection and Its Modulation by Mosquito Saliva |
| title_sort | innate immune response of primary human keratinocytes to west nile virus infection and its modulation by mosquito saliva |
| topic | West Nile virus keratinocytes mosquito saliva immunomodulation innate immune response |
| url | https://www.frontiersin.org/article/10.3389/fcimb.2018.00387/full |
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