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The Toll and IMD (immune deficiency) signaling pathways play a key role in the regulation of innate immunity in both the\n                    <jats:italic>Drosophila<\/jats:italic>\n                    model and blood-feeding insects. However, in ticks (chelicerates), immune determination for pathogen acquisition and transmission has not yet been fully explored. Here, we have mapped homologs of insect Toll and IMD pathways in the European tick\n                    <jats:italic>Ixodes ricinus<\/jats:italic>\n                    , an important vector of human and animal diseases. We show that most genes of the Toll pathway are well conserved, whereas the IMD pathway has been greatly reduced. We therefore investigated the functions of the individual components of the tick Toll pathway and found that, unlike in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    , it was specifically activated by Gram-negative bacteria. The activation of pathway induced the expression of\n                    <jats:italic>defensin<\/jats:italic>\n                    (\n                    <jats:italic>defIR<\/jats:italic>\n                    ), the first identified downstream effector gene of the tick Toll pathway.\n                    <jats:italic>Borrelia<\/jats:italic>\n                    , an atypical bacterium and causative agent of Lyme borreliosis, bypassed Toll-mediated recognition in\n                    <jats:italic>I<\/jats:italic>\n                    .\n                    <jats:italic>ricinus<\/jats:italic>\n                    and also resisted systemic effector molecules when the Toll pathway was activated by silencing its repressor\n                    <jats:italic>cactus<\/jats:italic>\n                    via RNA interference.\n                    <jats:italic>Babesia<\/jats:italic>\n                    , an apicomplexan parasite, also avoided Toll-mediated recognition. Strikingly, unlike\n                    <jats:italic>Borrelia<\/jats:italic>\n                    , the number of\n                    <jats:italic>Babesia<\/jats:italic>\n                    parasites reaching the salivary glands during tick infection was significantly reduced by knocking down\n                    <jats:italic>cactus<\/jats:italic>\n                    . The simultaneous silencing of\n                    <jats:italic>cactus<\/jats:italic>\n                    and\n                    <jats:italic>dorsal<\/jats:italic>\n                    resulted in greater infections and underscored the importance of tick immunity in regulating parasite infections in these important disease vectors.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1012743","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T13:22:11Z","timestamp":1734355331000},"page":"e1012743","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Activation of the tick Toll pathway to control infection of Ixodes ricinus by the apicomplexan parasite Babesia microti"],"prefix":"10.1371","volume":"20","author":[{"given":"Marie","family":"Jalovecka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Malandrin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Urbanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sazzad","family":"Mahmood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavla","family":"Snebergerova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriama","family":"Peklanska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Pavlasova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radek","family":"Sima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Kopacek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Perner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4607-5369","authenticated-orcid":true,"given":"Ondrej","family":"Hajdusek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"ppat.1012743.ref001","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3389\/fcimb.2013.00026","article-title":"Interaction 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Frolet","year":"2006","journal-title":"Immunity"},{"key":"ppat.1012743.ref026","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0092-8674(01)00267-7","article-title":"Conserved Role of a Complement-like Protein in Phagocytosis Revealed by dsRNA Knockout in Cultured Cells of the Mosquito, Anopheles gambiae","volume":"104","author":"EA Levashina","year":"2001","journal-title":"Cell"},{"key":"ppat.1012743.ref027","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/BF00222180","article-title":"Ultrastructural studies on sporogony of Babesia microti in salivary gland cells of the tick Ixodes dammini","volume":"231","author":"SJ Karakashian","year":"1983","journal-title":"Cell Tissue Res"},{"key":"ppat.1012743.ref028","doi-asserted-by":"crossref","first-page":"104234","DOI":"10.1016\/j.dci.2021.104234","article-title":"The role of complement in the tick cellular immune defense against the entomopathogenic fungus Metarhizium robertsii","volume":"126","author":"J Fiorotti","year":"2022","journal-title":"Dev Comp Immunol"},{"key":"ppat.1012743.ref029","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.smim.2014.05.003","article-title":"The Drosophila TNF ortholog Eiger: emerging physiological roles and evolution of the TNF system","volume":"26","author":"T Igaki","year":"2014","journal-title":"Semin Immunol"},{"key":"ppat.1012743.ref030","doi-asserted-by":"crossref","first-page":"1119879","DOI":"10.3389\/fimmu.2023.1119879","article-title":"Signaling events induced by lipopolysaccharide-activated Toll in response to bacterial infection in shrimp","volume":"14","author":"S Wang","year":"2023","journal-title":"Front Immunol"},{"key":"ppat.1012743.ref031","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/nature10640","article-title":"The genome of Tetranychus urticae reveals herbivorous pest adaptations","volume":"479","author":"M Grbi\u0107","year":"2011","journal-title":"Nature"},{"key":"ppat.1012743.ref032","doi-asserted-by":"crossref","first-page":"9978","DOI":"10.1073\/pnas.162345999","article-title":"Characterization of three alternatively spliced isoforms of the Rel\/NF-kappa B transcription factor Relish from the mosquito Aedes aegypti","volume":"99","author":"SW Shin","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1012743.ref033","doi-asserted-by":"crossref","first-page":"11420","DOI":"10.1073\/pnas.0504950102","article-title":"Immune signaling pathways regulating bacterial and malaria parasite infection of the mosquito Anopheles gambiae","volume":"102","author":"S Meister","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1012743.ref034","doi-asserted-by":"crossref","first-page":"e0070322","DOI":"10.1128\/mbio.00703-22","article-title":"The Unfolded-Protein Response Triggers the Arthropod Immune Deficiency Pathway","volume":"13","author":"LC 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Johnston","year":"1992","journal-title":"Cell"},{"key":"ppat.1012743.ref038","first-page":"20182207","article-title":"Functional crosstalk across IMD and Toll pathways: insight into the evolution of incomplete immune cascades","volume":"286","author":"Y Nishide","year":"2019","journal-title":"Proceedings Biol Sci"},{"key":"ppat.1012743.ref039","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.rinim.2012.03.002","article-title":"Antimicrobial peptide gene induction, involvement of Toll and IMD pathways and defense against bacteria in the red flour beetle, Tribolium castaneum","volume":"2","author":"K Yokoi","year":"2012","journal-title":"Results Immunol"},{"key":"ppat.1012743.ref040","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.3389\/fimmu.2019.01785","article-title":"The Two NF-\u03baB Pathways Regulating Bacterial and WSSV Infection of Shrimp","volume":"10","author":"C Li","year":"2019","journal-title":"Front 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