{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:02:27Z","timestamp":1790359347039,"version":"4.1.0"},"reference-count":56,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":194,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007688","name":"American University of Beirut","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007688","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008977","name":"Universit\u00e4t Ulm","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016263","name":"American University of Beirut University Research Board","doi-asserted-by":"publisher","award":["104631"],"award-info":[{"award-number":["104631"]}],"id":[{"id":"10.13039\/501100016263","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Current Research in Insect Science"],"published-print":{"date-parts":[[2026]]},"DOI":"10.1016\/j.cris.2026.100129","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T15:12:55Z","timestamp":1784128375000},"page":"100129","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Distinct roles of the Anopheles gambiae Imd\/Rel2 and Toll\/Rel1 pathways in resistance to systemic bacterial and fungal infections"],"prefix":"10.1016","volume":"10","author":[{"given":"Suheir","family":"Zeineddine","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sana","family":"Jaber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amani","family":"Audi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3078-6190","authenticated-orcid":false,"given":"Mike A.","family":"Osta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.cris.2026.100129_bib0001","doi-asserted-by":"crossref","first-page":"7063","DOI":"10.1128\/JB.00892-09","article-title":"The dlt operon of Bacillus cereus is required for resistance to cationic antimicrobial peptides and for virulence in insects","volume":"191","author":"Abi Khattar","year":"2009","journal-title":"J. Bacteriol."},{"key":"10.1016\/j.cris.2026.100129_bib0002","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2020.611220","article-title":"The fliK Gene Is required for the resistance of bacillus thuringiensis to antimicrobial peptides and virulence in drosophila melanogaster","volume":"11","author":"Attieh","year":"2020","journal-title":"Front. Microbiol."},{"key":"10.1016\/j.cris.2026.100129_bib0003","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1013527","article-title":"A PGRPLC1\/Rel2-F axis controls anopheles gambiae resistance to systemic infections with Gram-positive bacteria containing Lys-type peptidoglycan","volume":"21","author":"Audi","year":"2025","journal-title":"PLoS Pathog"},{"key":"10.1016\/j.cris.2026.100129_bib0004","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1146\/annurev-immunol-020711-075030","article-title":"Tolerance of infections","volume":"30","author":"Ayres","year":"2012","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.cris.2026.100129_bib0005","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.81116","article-title":"Hemocyte differentiation to the megacyte lineage enhances mosquito immunity against Plasmodium","volume":"11","author":"Barletta","year":"2022","journal-title":"Elife"},{"key":"10.1016\/j.cris.2026.100129_bib0006","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1186\/1471-2164-10-257","article-title":"Genome-wide transcriptomic profiling of Anopheles gambiae hemocytes reveals pathogen-specific signatures upon bacterial challenge and Plasmodium berghei infection","volume":"10","author":"Baton","year":"2009","journal-title":"BMC Genomics"},{"key":"10.1016\/j.cris.2026.100129_bib0007","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1093\/embo-reports\/kvf180","article-title":"Reverse genetics in the mosquito Anopheles gambiae: targeted disruption of the Defensin gene","volume":"3","author":"Blandin","year":"2002","journal-title":"EMBO Rep"},{"key":"10.1016\/j.cris.2026.100129_bib0008","doi-asserted-by":"crossref","first-page":"6315","DOI":"10.1038\/s41598-022-10190-3","article-title":"Genetics and immunity of anopheles response to the entomopathogenic fungus Metarhizium anisopliae overlap with immunity to Plasmodium","volume":"12","author":"Bukhari","year":"2022","journal-title":"Sci. Rep."},{"key":"10.1016\/j.cris.2026.100129_bib0009","doi-asserted-by":"crossref","first-page":"E2682","DOI":"10.1073\/pnas.1613917114","article-title":"Toll pathway is required for wound-induced expression of barrier repair genes in the drosophila epidermis","volume":"114","author":"Capilla","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"10.1016\/j.cris.2026.100129_bib0010","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/s41392-025-02264-1","article-title":"Pattern recognition receptors: function, regulation and therapeutic potential","volume":"10","author":"Chen","year":"2025","journal-title":"Signal. Transduct. Target Ther."},{"key":"10.1016\/j.cris.2026.100129_bib0011","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1004876","article-title":"An effector Peptide family required for drosophila toll-mediated immunity","volume":"11","author":"Clemmons","year":"2015","journal-title":"PLoS Pathog"},{"key":"10.1016\/j.cris.2026.100129_bib0012","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3389\/fimmu.2020.00009","article-title":"The Daisho peptides mediate drosophila defense against a subset of filamentous fungi","volume":"11","author":"Cohen","year":"2020","journal-title":"Front. Immunol."},{"key":"10.1016\/j.cris.2026.100129_bib0013","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1002458","article-title":"Engineered anopheles immunity to plasmodium infection","volume":"7","author":"Dong","year":"2011","journal-title":"PLoS Pathog"},{"key":"10.1016\/j.cris.2026.100129_bib0014","article-title":"The insect toll pathway activates antibacterial immunity against the citrus Huanglongbing pathogen","author":"Du","year":"2026","journal-title":"Nat. Commun."},{"key":"10.1016\/j.cris.2026.100129_bib0015","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1008194","article-title":"The mosquito melanization response requires hierarchical activation of non-catalytic clip domain serine protease homologs","volume":"15","author":"El Moussawi","year":"2019","journal-title":"PLoS Pathog"},{"key":"10.1016\/j.cris.2026.100129_bib0016","doi-asserted-by":"crossref","first-page":"33159","DOI":"10.1016\/S0021-9258(20)30111-3","article-title":"Insect immunity. Septic injury of drosophila induces the synthesis of a potent antifungal peptide with sequence homology to plant antifungal peptides","volume":"269","author":"Fehlbaum","year":"1994","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.cris.2026.100129_bib0017","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.immuni.2006.08.019","article-title":"Boosting NF-kappaB-dependent basal immunity of Anopheles gambiae aborts development of Plasmodium berghei","volume":"25","author":"Frolet","year":"2006","journal-title":"Immunity"},{"key":"10.1016\/j.cris.2026.100129_bib0018","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1002737","article-title":"Anopheles Imd pathway factors and effectors in infection intensity-dependent anti-Plasmodium action","volume":"8","author":"Garver","year":"2012","journal-title":"PLoS Pathog"},{"key":"10.1016\/j.cris.2026.100129_bib0019","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1000335","article-title":"Caspar controls resistance to Plasmodium falciparum in diverse anopheline species","volume":"5","author":"Garver","year":"2009","journal-title":"PLoS Pathog"},{"key":"10.1016\/j.cris.2026.100129_bib0020","article-title":"Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach","volume":"8","author":"Hanson","year":"2019","journal-title":"Elife"},{"key":"10.1016\/j.cris.2026.100129_bib0021","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1146\/annurev-micro-101923-100221","article-title":"The antimicrobial and host defense peptides of drosophila melanogaster","volume":"79","author":"Hanson","year":"2025","journal-title":"Annu. Rev. Microbiol."},{"key":"10.1016\/j.cris.2026.100129_bib0022","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1186\/s12864-024-10153-0","article-title":"The transcriptional response in mosquitoes distinguishes between fungi and bacteria but not Gram types","volume":"25","author":"Hixson","year":"2024","journal-title":"BMC Genomics"},{"key":"10.1016\/j.cris.2026.100129_bib0023","article-title":"A toll pathway effector protects drosophila specifically from distinct toxins secreted by a fungus or a bacterium","volume":"120","author":"Huang","year":"2023","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"10.1016\/j.cris.2026.100129_bib0024","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.3389\/fmicb.2017.01437","article-title":"DltX of bacillus thuringiensis is essential for D-alanylation of teichoic acids and resistance to antimicrobial response in insects","volume":"8","author":"Kamar","year":"2017","journal-title":"Front. Microbiol."},{"key":"10.1016\/j.cris.2026.100129_bib0025","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1016\/S0960-9822(00)00833-2","article-title":"Caenorhabditis elegans is a model host for Salmonella typhimurium","volume":"10","author":"Labrousse","year":"2000","journal-title":"Current Biology"},{"key":"10.1016\/j.cris.2026.100129_bib0026","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S0092-8674(00)80172-5","article-title":"The dorsoventral regulatory gene cassette spatzle\/Toll\/cactus controls the potent antifungal response in Drosophila adults","volume":"86","author":"Lemaitre","year":"1996","journal-title":"Cell"},{"key":"10.1016\/j.cris.2026.100129_bib0027","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1111\/j.1432-1033.1995.694_2.x","article-title":"Metchnikowin, a novel immune-inducible proline-rich peptide from drosophila with antibacterial and antifungal properties","volume":"233","author":"Levashina","year":"1995","journal-title":"Eur. J. Biochem."},{"key":"10.1016\/j.cris.2026.100129_bib0028","doi-asserted-by":"crossref","DOI":"10.1038\/s44319-025-00559-6","article-title":"Distinct Bomanins at the Drosophila 55C locus function in resistance and resilience to infections","author":"Lou","year":"2026","journal-title":"EMBO Rep"},{"key":"10.1016\/j.cris.2026.100129_bib0029","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1111\/j.1365-2583.2006.00661.x","article-title":"Expression of immune responsive genes in cell lines from two different Anopheline species","volume":"15","author":"Luna","year":"2006","journal-title":"Insect. Mol. Biol"},{"key":"10.1016\/j.cris.2026.100129_bib0030","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.mimet.2009.02.011","article-title":"Fluorescent reporters for staphylococcus aureus","volume":"77","author":"Malone","year":"2009","journal-title":"J. Microbiol. Methods."},{"key":"10.1016\/j.cris.2026.100129_bib0031","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1126\/science.1214935","article-title":"Disease tolerance as a defense strategy","volume":"335","author":"Medzhitov","year":"2012","journal-title":"Science"},{"key":"10.1016\/j.cris.2026.100129_bib0032","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1000542","article-title":"Anopheles gambiae PGRPLC-mediated defense against bacteria modulates infections with malaria parasites","volume":"5","author":"Meister","year":"2009","journal-title":"PLoS Pathog"},{"key":"10.1016\/j.cris.2026.100129_bib0033","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":"Meister","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"10.1016\/j.cris.2026.100129_bib0034","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1000069","article-title":"Conserved mosquito\/parasite interactions affect development of Plasmodium falciparum in Africa","volume":"4","author":"Mendes","year":"2008","journal-title":"PLoS Pathog"},{"key":"10.1016\/j.cris.2026.100129_bib0035","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1000576","article-title":"Fine pathogen discrimination within the APL1 gene family protects anopheles gambiae against human and rodent malaria species","volume":"5","author":"Mitri","year":"2009","journal-title":"PLoS Pathog"},{"key":"10.1016\/j.cris.2026.100129_bib0036","doi-asserted-by":"crossref","DOI":"10.3389\/fcimb.2023.891577","article-title":"A zone-of-inhibition assay to screen for humoral antimicrobial activity in mosquito hemolymph","volume":"13","author":"Morejon","year":"2023","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"10.1016\/j.cris.2026.100129_bib0037","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2425863122","article-title":"The expanded immunoregulatory protease network in mosquitoes is governed by gene coexpression","volume":"122","author":"Morejon","year":"2025","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"10.1016\/j.cris.2026.100129_bib0038","doi-asserted-by":"crossref","first-page":"21270","DOI":"10.1073\/pnas.0909463106","article-title":"Discovery of Plasmodium modulators by genome-wide analysis of circulating hemocytes in Anopheles gambiae","volume":"106","author":"Pinto","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"10.1016\/j.cris.2026.100129_bib0039","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1126\/science.abc0322","article-title":"Mosquito cellular immunity at single-cell resolution","volume":"369","author":"Raddi","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.cris.2026.100129_bib0040","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2021.627976","article-title":"Use of Clodronate Liposomes to Deplete Phagocytic Immune Cells in Drosophila melanogaster and Aedes aegypti","volume":"9","author":"Ramesh Kumar","year":"2021","journal-title":"Front. Cell. Dev. Biol."},{"key":"10.1016\/j.cris.2026.100129_bib0041","doi-asserted-by":"crossref","DOI":"10.1002\/mbo3.1304","article-title":"Improved fluorescent Listeria spp. biosensors for analysis of antimicrobials by flow cytometry","volume":"11","author":"Reich","year":"2022","journal-title":"Microbiologyopen"},{"key":"10.1016\/j.cris.2026.100129_bib0042","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.dci.2018.04.008","article-title":"The interplay between dose and immune system activation determines fungal infection outcome in the African malaria mosquito, anopheles gambiae","volume":"85","author":"Rhodes","year":"2018","journal-title":"Dev. Comp. Immunol."},{"issue":"11","key":"10.1016\/j.cris.2026.100129_bib0043","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0003672","article-title":"Anopheles gambiae APL1 is a family of variable LRR proteins required for Rel1-mediated protection from the malaria parasite, Plasmodium berghei","volume":"3","author":"Riehle","year":"2008","journal-title":"PLoS One"},{"key":"10.1016\/j.cris.2026.100129_bib0044","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.107030.3","article-title":"Layers of immunity: deconstructing the drosophila effector response","volume":"14","author":"Ryckebusch","year":"2025","journal-title":"Elife"},{"key":"10.1016\/j.cris.2026.100129_bib0045","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2531951123","article-title":"Single-cell insights: mosquito Toll activation enhances granulocyte differentiation and immune surveillance via Notch suppression","volume":"123","author":"Saha","year":"2026","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"10.1016\/j.cris.2026.100129_bib0046","doi-asserted-by":"crossref","first-page":"39388","DOI":"10.1074\/jbc.M608912200","article-title":"A toll receptor and a cytokine, Toll5A and Spz1C, are involved in toll antifungal immune signaling in the mosquito Aedes aegypti","volume":"281","author":"Shin","year":"2006","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.cris.2026.100129_bib0047","doi-asserted-by":"crossref","first-page":"16499","DOI":"10.1074\/jbc.M500711200","article-title":"REL1, a homologue of Drosophila dorsal, regulates toll antifungal immune pathway in the female mosquito Aedes aegypti","volume":"280","author":"Shin","year":"2005","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.cris.2026.100129_bib0048","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.3002967","article-title":"Cell wall components of gut commensal bacteria stimulate peritrophic matrix formation in malaria vector mosquitoes through activation of the IMD pathway","volume":"23","author":"Song","year":"2025","journal-title":"PLoS Biol"},{"key":"10.1016\/j.cris.2026.100129_bib0049","article-title":"OTU7B modulates the mosquito immune response to Beauveria bassiana Infection via Deubiquitination of the toll adaptor TRAF4","volume":"11","author":"Wang","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"10.1016\/j.cris.2026.100129_bib0050","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1126\/science.1139862","article-title":"Evolutionary dynamics of immune-related genes and pathways in disease-vector mosquitoes","volume":"316","author":"Waterhouse","year":"2007","journal-title":"Science"},{"key":"10.1016\/j.cris.2026.100129_bib0051","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1000098","article-title":"The Aedes aegypti toll pathway controls dengue virus infection","volume":"4","author":"Xi","year":"2008","journal-title":"PLoS Pathog"},{"key":"10.1016\/j.cris.2026.100129_bib0052","doi-asserted-by":"crossref","DOI":"10.1098\/rsob.220111","article-title":"The immune deficiency and c-Jun N-terminal kinase pathways drive the functional integration of the immune and circulatory systems of mosquitoes","volume":"12","author":"Yan","year":"2022","journal-title":"Open Biol"},{"key":"10.1016\/j.cris.2026.100129_bib0053","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1003029","article-title":"The mosquito melanization response is implicated in defense against the entomopathogenic fungus Beauveria bassiana","volume":"8","author":"Yassine","year":"2012","journal-title":"PLoS Pathog"},{"key":"10.1016\/j.cris.2026.100129_bib0054","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1462-5822.2009.01388.x","article-title":"Anopheles gambiae innate immunity","volume":"12","author":"Yassine","year":"2010","journal-title":"Cell. Microbiol."},{"key":"10.1016\/j.cris.2026.100129_bib0055","first-page":"1","article-title":"CLIPA7 exhibits pleiotropic roles in the anopheles gambiae immune response","author":"Zakhia","year":"2022","journal-title":"J. Innate Immun."},{"key":"10.1016\/j.cris.2026.100129_bib0056","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2025.116282","article-title":"The major role of the REL2\/NF-kappaB pathway in the regulation of midgut bacterial homeostasis in the malaria vector Anopheles gambiae","volume":"44","author":"Zakovic","year":"2025","journal-title":"Cell Rep"}],"container-title":["Current Research in Insect Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666515826000089?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2666515826000089?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:47:54Z","timestamp":1790358474000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2666515826000089"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":56,"alternative-id":["S2666515826000089"],"URL":"https:\/\/doi.org\/10.1016\/j.cris.2026.100129","relation":{},"ISSN":["2666-5158"],"issn-type":[{"value":"2666-5158","type":"print"}],"subject":[],"published":{"date-parts":[[2026]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Distinct roles of the Anopheles gambiae Imd\/Rel2 and Toll\/Rel1 pathways in resistance to systemic bacterial and fungal infections","name":"articletitle","label":"Article Title"},{"value":"Current Research in Insect Science","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.cris.2026.100129","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"100129"}}