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Artemisinin and its derivatives are first-line drugs for the treatment of\n                      <jats:italic>Plasmodium falciparum<\/jats:italic>\n                      malaria. In mammals, artemisinin exhibits potent anti-inflammatory and immunoregulatory properties. However, it is unclear whether artemisinin plays a regulatory role in the innate immunity of mosquitoes, thereby affecting the development of\n                      <jats:italic>Plasmodium<\/jats:italic>\n                      in\n                      <jats:italic>Anopheles<\/jats:italic>\n                      when artemisinin and its metabolites enter mosquitoes. This study aims to determine the effect of dihydroartemisinin (DHA), a first-generation semisynthetic derivative of artemisinin, on innate immunity and malaria vector competence of\n                      <jats:italic>Anopheles stephensi<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Anopheles stephensi<\/jats:italic>\n                      was fed\n                      <jats:italic>Plasmodium<\/jats:italic>\n                      -infected mice treated with DHA via gavage,\n                      <jats:italic>Plasmodium<\/jats:italic>\n                      -infected blood containing DHA in vitro, or DHA-containing sugar, followed by\n                      <jats:italic>Plasmodium yoelii<\/jats:italic>\n                      infection. The engorged female mosquitoes were separated and dissected 8 and 17\u00a0days after infection.\n                      <jats:italic>Plasmodium<\/jats:italic>\n                      oocysts and sporozoites were counted and compared between the control and DHA-treated groups. Additionally, total RNA and proteins were extracted from engorged mosquitoes 24 and 72\u00a0h post infection (hpi). Real-time polymerase chain reaction (PCR) and western blotting were performed to detect the transcriptional levels and protein expression of immune molecules in mosquitoes. Finally, the Toll signaling pathway was inhibited via RNA interference and the infection density was analyzed to confirm the role of the Toll signaling pathway in the effect of DHA on the vector competence of mosquitoes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      DHA treatment via different approaches significantly reduced the number of\n                      <jats:italic>Plasmodium<\/jats:italic>\n                      oocysts and sporozoites in mosquitoes. The transcriptional levels of anti-\n                      <jats:italic>Plasmodium<\/jats:italic>\n                      immune genes (including\n                      <jats:italic>TEP1<\/jats:italic>\n                      ,\n                      <jats:italic>LRIM1<\/jats:italic>\n                      , and\n                      <jats:italic>APL1C<\/jats:italic>\n                      ), Toll pathway genes (including\n                      <jats:italic>Tube<\/jats:italic>\n                      ,\n                      <jats:italic>MyD88<\/jats:italic>\n                      , and\n                      <jats:italic>Rel1<\/jats:italic>\n                      ), and the effector\n                      <jats:italic>defensin 1<\/jats:italic>\n                      were upregulated by DHA treatment at 24 and 72 hpi. TEP1 and Rel1 protein expression was significantly induced under DHA treatment. However, Rel1 knockdown in DHA-treated mosquitoes abrogated DHA-mediated refractoriness to\n                      <jats:italic>Plasmodium<\/jats:italic>\n                      infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      DHA treatment effectively inhibited the development of\n                      <jats:italic>P. yoelii<\/jats:italic>\n                      in\n                      <jats:italic>A. stephensi<\/jats:italic>\n                      by upregulating mosquitoes\u2019 Toll signaling pathway, thereby influencing the susceptibility of\n                      <jats:italic>Anopheles<\/jats:italic>\n                      to\n                      <jats:italic>Plasmodium<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s13071-024-06497-x","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:05:11Z","timestamp":1728000311000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dihydroartemisinin suppresses the susceptibility of Anopheles stephensi to Plasmodium yoelii by activating the Toll signaling pathway"],"prefix":"10.1186","volume":"17","author":[{"given":"Tingting","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caizhi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,4]]},"reference":[{"key":"6497_CR1","unstructured":"WHO. 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