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Herein, we examined a collection of Drosophila melanogaster knockout (KO) lines generated in our laboratory, lacking key genes involved in transsulfuration (cbs, cse) and sulfide metabolism (tst1), to elucidate the role of this adaptive system in immunity. Genetic ablation of these pathways results in profound H2S deficiency and hyperhomocysteinemia, leading to chronic oxidative stress. This leads to constitutive activation of major immune pathways\u2014including IMD, Toll, and JAK-STAT\u2014even in the absence of infection, a hallmark of chronic inflammation. Indeed, transcriptomic analysis and qRT-PCR studies revealed significant upregulation of these pathways in double (cbs; cse) and triple (cbs; cse; tst1) KO flies under control conditions. Following septic injury with Bacillus subtilis, double and triple KO flies exhibited increased expression of antimicrobial peptides (AMPs) and pattern recognition receptors compared to control and TST1-\/- single KO lines. Notably, double and triple KO lines showed more prolonged immune activation. The triple KO flies exhibited the worst survival rate following septic injury. These results demonstrate that H2S deficiency causes chronic inflammation through the sustained activation of immune pathways, highlighting sulfur metabolism as a crucial regulator of homeostasis and innate immunity in Drosophila.<\/jats:p>","DOI":"10.3390\/antiox15070881","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T08:08:34Z","timestamp":1784189314000},"page":"881","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Knockouts of Sulfur Metabolism Genes Induce Chronic Inflammation and Immune Dysregulation in Drosophila melanogaster"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4850-5932","authenticated-orcid":false,"given":"Victoria","family":"Shilova","sequence":"first","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Rezvykh","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9315-9880","authenticated-orcid":false,"given":"Victoria","family":"Aristova","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"},{"name":"Moscow Center for Advanced Studies, 123592 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2635-9279","authenticated-orcid":false,"given":"Artem","family":"Davletshin","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Andreeva","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2992-8752","authenticated-orcid":false,"given":"Ksenia","family":"Ponomareva","sequence":"additional","affiliation":[{"name":"Center for Master\u2019s Programs, Master\u2019s Program \u201cSynthetic Biology and Biodesign\u201d, First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Garbuz","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Evgen\u2019ev","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5982-941X","authenticated-orcid":false,"given":"Olga","family":"Zatsepina","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen Recognition and Innate Immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"ref_2","first-page":"2759513","article-title":"\u201cThe Good, the Bad and the Ugly\u201d: Interplay of Innate Immunity and Inflammation","volume":"2022","year":"2022","journal-title":"Cell. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41423-022-00840-x","article-title":"Immunometabolism at the Intersection of Metabolic Signaling, Cell Fate, and Systems Immunology","volume":"19","author":"Chi","year":"2022","journal-title":"Cell. Mol. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6022","DOI":"10.1073\/pnas.1703576114","article-title":"Mechanism of H2 S-Mediated Protection against Oxidative Stress in Escherichia coli","volume":"114","author":"Mironov","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1089\/ars.2014.5901","article-title":"Anti-Inflammatory and Cytoprotective Actions of Hydrogen Sulfide: Translation to Therapeutics","volume":"22","author":"Wallace","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"131","DOI":"10.2183\/pjab.91.131","article-title":"Hydrogen Sulfide and Polysulfides as Signaling Molecules","volume":"91","author":"Kimura","year":"2015","journal-title":"Proc. Jpn. Acad. Ser. B Phys. Biol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1074\/jbc.RA117.000826","article-title":"Thiosulfate Sulfurtransferase-like Domain\u2013Containing 1 Protein Interacts with Thioredoxin","volume":"293","author":"Libiad","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4739","DOI":"10.1021\/bi500650h","article-title":"Biosynthesis of a Central Intermediate in Hydrogen Sulfide Metabolism by a Novel Human Sulfurtransferase and Its Yeast Ortholog","volume":"53","author":"Melideo","year":"2014","journal-title":"Biochemistry"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nagahara, N., Tanaka, M., Tanaka, Y., and Ito, T. (2019). Novel Characterization of Antioxidant Enzyme, 3-Mercaptopyruvate Sulfurtransferase-Knockout Mice: Overexpression of the Evolutionarily-Related Enzyme Rhodanese. Antioxidants, 8.","DOI":"10.3390\/antiox8050116"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1152\/physrev.00028.2021","article-title":"Physiological Roles of Hydrogen Sulfide in Mammalian Cells, Tissues, and Organs","volume":"103","author":"Cirino","year":"2023","journal-title":"Physiol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"105119","DOI":"10.1016\/j.phrs.2020.105119","article-title":"Hydrogen Sulfide: An Endogenous Regulator of the Immune System","volume":"161","author":"Dilek","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s00203-026-04903-9","article-title":"Insect Immunity Unveiled: Exploring the Molecular and Cellular Defenses against Microbial Threats","volume":"208","author":"Makkar","year":"2026","journal-title":"Arch. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.1093\/emboj\/21.11.2568","article-title":"The Toll and Imd Pathways Are the Major Regulators of the Immune Response in Drosophila","volume":"21","author":"Spellman","year":"2002","journal-title":"EMBO J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1146\/annurev.immunol.25.022106.141615","article-title":"The Host Defense of Drosophila melanogaster","volume":"25","author":"Lemaitre","year":"2007","journal-title":"Annu. Rev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"649","DOI":"10.4049\/jimmunol.1002302","article-title":"The Drosophila Toll Signaling Pathway","volume":"186","author":"Valanne","year":"2011","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Shilova, V.Y., Garbuz, D.G., Chuvakova, L.N., Rezvykh, A.P., Funikov, S.Y., Davletshin, A.I., Sorokina, S.Y., Nikitina, E.A., Gorenskaya, O., and Evgen\u2019ev, M.B. (2025). The Biological Consequences of the Knockout of Genes Involved in the Synthesis and Metabolism of H2S in Drosophila Melanogaster. Antioxidants, 14.","DOI":"10.3390\/antiox14060693"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"108368","DOI":"10.1016\/j.celrep.2020.108368","article-title":"Intramacrophage ROS Primes the Innate Immune System via JAK\/STAT and Toll Activation","volume":"33","author":"Chakrabarti","year":"2020","journal-title":"Cell Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.cca.2019.08.015","article-title":"Heat Shock Proteins in Infection","volume":"498","author":"Bolhassani","year":"2019","journal-title":"Clin. Chim. Acta"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Gan, T., Fan, L., Zhao, L., Misra, M., Liu, M., Zhang, M., and Su, Y. (2021). JNK Signaling in Drosophila Aging and Longevity. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179649"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Darby, A.M., and Lazzaro, B.P. (2023). Interactions between Innate Immunity and Insulin Signaling Affect Resistance to Infection in Insects. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1276357"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101654","DOI":"10.1016\/j.redox.2020.101654","article-title":"Genome-wide transcriptional effects of deletions of sulphur metabolism genes in Drosophila melanogaster","volume":"36","author":"Zatsepina","year":"2020","journal-title":"Redox Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e28298","DOI":"10.7554\/eLife.28298","article-title":"Stochastic Variation in the Initial Phase of Bacterial Infection Predicts the Probability of Survival in D. Melanogaster","volume":"6","author":"Duneau","year":"2017","journal-title":"eLife"},{"key":"ref_23","first-page":"52613","article-title":"Systemic Bacterial Infection and Immune Defense Phenotypes in Drosophila Melanogaster","volume":"99","author":"Khalil","year":"2015","journal-title":"J. Vis. Exp."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s13205-013-0177-6","article-title":"Specific Oligonucleotide Primers for Detection of Endoglucanase Positive Bacillus Subtilis by PCR","volume":"4","author":"Ashe","year":"2014","journal-title":"3 Biotech"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"RP107030","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":"ref_26","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A Flexible Trimmer for Illumina Sequence Data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast Universal RNA-Seq Aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map Format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: An Efficient General Purpose Program for Assigning Sequence Reads to Genomic Features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor Package for Differential Expression Analysis of Digital Gene Expression Data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R Package for Comparing Biological Themes Among Gene Clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS A J. Integr. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Schlamp, F., Delbare, S.Y.N., Early, A.M., Wells, M.T., Basu, S., and Clark, A.G. (2021). Dense time-course gene expression profiling of the Drosophila melanogaster innate immune response. BMC Genom., 22.","DOI":"10.1186\/s12864-021-07593-3"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.dci.2013.06.006","article-title":"Peptidoglycan Recognition Proteins in Drosophila Immunity","volume":"42","author":"Kurata","year":"2014","journal-title":"Dev. Comp. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.chom.2008.04.002","article-title":"The Drosophila Peptidoglycan Recognition Protein PGRP-LF Blocks PGRP-LC and IMD\/JNK Pathway Activation","volume":"3","author":"Maillet","year":"2008","journal-title":"Cell Host Microbe"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5413","DOI":"10.4049\/jimmunol.180.8.5413","article-title":"Pirk Is a Negative Regulator of the Drosophila Imd Pathway","volume":"180","author":"Kleino","year":"2008","journal-title":"J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4690","DOI":"10.1038\/sj.emboj.7600466","article-title":"Peptidoglycan Recognition Protein (PGRP)-LE and PGRP-LC Act Synergistically in Drosophila Immunity","volume":"23","author":"Takehana","year":"2004","journal-title":"EMBO J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.immuni.2016.10.029","article-title":"PGRP-SD, an Extracellular Pattern-Recognition Receptor, Enhances Peptidoglycan-Mediated Activation of the Drosophila Imd Pathway","volume":"45","author":"Iatsenko","year":"2016","journal-title":"Immunity"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zaidman-R\u00e9my, A., Poidevin, M., Herv\u00e9, M., Welchman, D.P., Paredes, J.C., Fahlander, C., Steiner, H., Mengin-Lecreulx, D., and Lemaitre, B. (2011). Drosophila Immunity: Analysis of PGRP-SB1 Expression, Enzymatic Activity and Function. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017231"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1073\/pnas.1516122113","article-title":"Cytokine Diedel and a Viral Homologue Suppress the IMD Pathway in Drosophila","volume":"113","author":"Lamiable","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.immuni.2006.02.012","article-title":"The Drosophila Amidase PGRP-LB Modulates the Immune Response to Bacterial Infection","volume":"24","author":"Poidevin","year":"2006","journal-title":"Immunity"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Bischoff, V., Vignal, C., Duvic, B., Boneca, I.G., Hoffmann, J.A., and Royet, J. (2006). Downregulation of the Drosophila Immune Response by Peptidoglycan-Recognition Proteins SC1 and SC2. PLoS Pathog., 2.","DOI":"10.1371\/journal.ppat.0020014"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8738","DOI":"10.1074\/jbc.M117.788158","article-title":"Innate Immune Signaling in Drosophila Is Regulated by Transforming Growth Factor \u03b2 (TGF\u03b2)-Activated Kinase (Tak1)-Triggered Ubiquitin Editing","volume":"292","author":"Chen","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.micinf.2005.03.014","article-title":"Functional Analysis of Immune Response Genes in Drosophila Identifies JNK Pathway as a Regulator of Antimicrobial Peptide Gene Expression in S2 Cells","volume":"7","author":"Kallio","year":"2005","journal-title":"Microbes Infect."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5294","DOI":"10.1038\/sj.emboj.7601401","article-title":"JNK- and Fos-regulated Mmp1 Expression Cooperates with Ras to Induce Invasive Tumors in Drosophila","volume":"25","author":"Uhlirova","year":"2006","journal-title":"EMBO J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.ibmb.2005.10.004","article-title":"Immune Challenge Induces N-Terminal Cleavage of the Drosophila Serpin Necrotic","volume":"36","author":"Pelte","year":"2006","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"113642","DOI":"10.1016\/j.celrep.2023.113642","article-title":"Suppression of Drosophila antifungal immunity by a parasite effector via blocking GNBP3 and GNBP-like 3, the dual receptors for \u03b2-glucans","volume":"43","author":"Lu","year":"2024","journal-title":"Cell Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1038\/emboj.2011.476","article-title":"Genetic Evidence of a Redox-dependent Systemic Wound Response via Hayan Protease-Phenoloxidase System in Drosophila","volume":"31","author":"Nam","year":"2012","journal-title":"EMBO J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/B978-0-12-386471-0.00011-0","article-title":"The Drosophila Serpins","volume":"Volume 499","author":"Reichhart","year":"2011","journal-title":"Methods in Enzymology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.biochi.2015.10.007","article-title":"Drosophila Melanogaster Clip-Domain Serine Proteases: Structure, Function and Regulation","volume":"122","author":"Veillard","year":"2016","journal-title":"Biochimie"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"eadk2756","DOI":"10.1126\/sciadv.adk2756","article-title":"An Evolutionarily Conserved Serine Protease Network Mediates Melanization and Toll Activation in Drosophila","volume":"9","author":"Shan","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"EMBR202256036","DOI":"10.15252\/embr.202256036","article-title":"The Toll Pathway Mediates Drosophila Resilience to Aspergillus Mycotoxins through Specific Bomanins","volume":"24","author":"Xu","year":"2023","journal-title":"EMBO Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/s44319-025-00559-6","article-title":"Distinct Bomanins at the Drosophila 55C Locus Function in Resistance and Resilience to Infections","volume":"27","author":"Lou","year":"2026","journal-title":"EMBO Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1159\/000489831","article-title":"Short-Form Bomanins Mediate Humoral Immunity in Drosophila","volume":"10","author":"Lindsay","year":"2018","journal-title":"J. Innate Immun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"115082","DOI":"10.1016\/j.celrep.2024.115082","article-title":"A Nonsecretory Antimicrobial Peptide Mediates Inflammatory Organ Damage in Drosophila Renal Tubules","volume":"44","author":"Oi","year":"2025","journal-title":"Cell Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.tcb.2005.10.001","article-title":"Tip of Another Iceberg: Drosophila Serpins","volume":"15","author":"Reichhart","year":"2005","journal-title":"Trends Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/s41531-025-00899-z","article-title":"Longitudinal Multi-Omics in Alpha-Synuclein Drosophila Model Discriminates Disease- from Age-Associated Pathologies in Parkinson\u2019s Disease","volume":"11","author":"Moore","year":"2025","journal-title":"npj Park. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Handke, B., Poernbacher, I., Goetze, S., Ahrens, C.H., Omasits, U., Marty, F., Simigdala, N., Meyer, I., Wollscheid, B., and Brunner, E. (2013). The Hemolymph Proteome of Fed and Starved Drosophila Larvae. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067208"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.devcel.2008.08.017","article-title":"A Serpin That Regulates Immune Melanization in the Respiratory System of Drosophila","volume":"15","author":"Tang","year":"2008","journal-title":"Dev. Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ydbio.2008.08.030","article-title":"Drosophila Serpin-28D Regulates Hemolymph Phenoloxidase Activity and Adult Pigmentation","volume":"323","author":"Scherfer","year":"2008","journal-title":"Dev. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Shokal, U., and Eleftherianos, I. (2017). Evolution and Function of Thioester-Containing Proteins and the Complement System in the Innate Immune Response. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00759"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"11427","DOI":"10.1073\/pnas.97.21.11427","article-title":"Constitutive Expression of a Complement-like Protein in Toll and JAK Gain-of-Function Mutants of Drosophila","volume":"97","author":"Lagueux","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Dost\u00e1lov\u00e1, A., Rommelaere, S., Poidevin, M., and Lemaitre, B. (2017). Thioester-Containing Proteins Regulate the Toll Pathway and Play a Role in Drosophila Defence against Microbial Pathogens and Parasitoid Wasps. BMC Biol., 15.","DOI":"10.1186\/s12915-017-0408-0"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Garver, L.S., De Almeida Oliveira, G., and Barillas-Mury, C. (2013). The JNK Pathway Is a Key Mediator of Anopheles Gambiae Antiplasmodial Immunity. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003622"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1159\/000321554","article-title":"Analysis of Thioester-Containing Proteins during the Innate Immune Response of Drosophila Melanogaster","volume":"3","author":"Hetru","year":"2011","journal-title":"J. Innate Immun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.imlet.2020.06.017","article-title":"JNK Signaling in Drosophila Immunity and Homeostasis","volume":"226","author":"Eleftherianos","year":"2020","journal-title":"Immunol. Lett."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"14344","DOI":"10.1038\/s41598-020-71291-5","article-title":"JNK Signaling Regulates Oviposition in the Malaria Vector Anopheles Gambiae","volume":"10","author":"Peirce","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1159\/000450610","article-title":"Thioester-Containing Protein-4 Regulates the Drosophila Immune Signaling and Function against the Pathogen Photorhabdus","volume":"9","author":"Shokal","year":"2017","journal-title":"J. Innate Immun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"EMBR202052262","DOI":"10.15252\/embr.202052262","article-title":"A Secreted Factor NimrodB4 Promotes the Elimination of Apoptotic Corpses by Phagocytes in Drosophila","volume":"22","author":"Petrignani","year":"2021","journal-title":"EMBO Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3399","DOI":"10.1111\/febs.15237","article-title":"The Adipokine NimrodB5 Regulates Peripheral Hematopoiesis in Drosophila","volume":"287","author":"Ramond","year":"2020","journal-title":"FEBS J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"103468","DOI":"10.1016\/j.dci.2019.103468","article-title":"Pattern Recognition Receptors in Drosophila Immune Responses","volume":"102","author":"Lu","year":"2020","journal-title":"Dev. Comp. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/S1074-7613(01)00249-7","article-title":"Drosophila Scavenger Receptor CI Is a Pattern Recognition Receptor for Bacteria","volume":"15","author":"Pearson","year":"2001","journal-title":"Immunity"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Li, X.-J., Yang, L., Li, D., Zhu, Y.-T., Wang, Q., and Li, W.-W. (2018). Pathogen-Specific Binding Soluble Down Syndrome Cell Adhesion Molecule (Dscam) Regulates Phagocytosis via Membrane-Bound Dscam in Crab. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00801"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.1111\/febs.14857","article-title":"Two Nimrod receptors, NimC1 and Eater, synergistically contribute to bacterial phagocytosis in Drosophila melanogaster","volume":"286","author":"Melcarne","year":"2019","journal-title":"FEBS J."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.cell.2005.08.034","article-title":"Eater, a Transmembrane Protein Mediating Phagocytosis of Bacterial Pathogens in Drosophila","volume":"123","author":"Kocks","year":"2005","journal-title":"Cell"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Khan, S.A., Kojour, M.A.M., and Han, Y.S. (2023). Recent Trends in Insect Gut Immunity. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1272143"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1146\/annurev-genet-111212-133343","article-title":"The Digestive Tract of Drosophila melanogaster","volume":"47","author":"Lemaitre","year":"2013","journal-title":"Annu. Rev. Genet."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e00094-19","DOI":"10.1128\/IAI.00094-19","article-title":"Participation of the Serine Protease Jonah66Ci in the Drosophila Antinematode Immune Response","volume":"87","author":"Yadav","year":"2019","journal-title":"Infect. Immun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"14057","DOI":"10.1128\/JVI.02320-14","article-title":"Drosophila C Virus Systemic Infection Leads to Intestinal Obstruction","volume":"88","author":"Chtarbanova","year":"2014","journal-title":"J. Virol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.semcdb.2022.04.002","article-title":"Regulating Metabolism to Shape Immune Function: Lessons from Drosophila","volume":"138","author":"Bland","year":"2023","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.cmet.2008.02.012","article-title":"Opposing Effects of Dietary Protein and Sugar Regulate a Transcriptional Target of Drosophila Insulin-like Peptide Signaling","volume":"7","author":"Buch","year":"2008","journal-title":"Cell Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"25788","DOI":"10.3390\/ijms161025788","article-title":"Hormonal Regulation of Response to Oxidative Stress in Insects\u2014An Update","volume":"16","author":"Krishnan","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1016\/j.celrep.2018.02.033","article-title":"Innate Immune Signaling in Drosophila Blocks Insulin Signaling by Uncoupling PI(3,4,5)P3 Production and Akt Activation","volume":"22","author":"Roth","year":"2018","journal-title":"Cell Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1016\/j.cub.2024.02.049","article-title":"A Humoral Stress Response Protects Drosophila Tissues from Antimicrobial Peptides","volume":"34","author":"Rommelaere","year":"2024","journal-title":"Curr. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s12192-020-01074-4","article-title":"Age-Dependent Expression Profiles of Two Adaptogenic Systems and Thermotolerance in Drosophila Melanogaster","volume":"25","author":"Shilova","year":"2020","journal-title":"Cell Stress Chaperones"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1006\/bbrc.2001.5067","article-title":"A Family of Turandot-Related Genes in the Humoral Stress Response of Drosophila","volume":"284","author":"Ekengren","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"104456","DOI":"10.1016\/j.jinsphys.2022.104456","article-title":"A Functional Study of the Role of Turandot Genes in Drosophila Melanogaster: An Emerging Candidate Mechanism for Inducible Heat Tolerance","volume":"143","author":"Amstrup","year":"2022","journal-title":"J. Insect Physiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/S1534-5807(03)00244-2","article-title":"Signaling Role of Hemocytes in Drosophila JAK\/STAT-Dependent Response to Septic Injury","volume":"5","author":"Agaisse","year":"2003","journal-title":"Dev. Cell"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"10394","DOI":"10.1038\/s41598-017-10740-0","article-title":"Ancestry & Molecular Evolutionary Analyses of Heat Shock Protein 47 kDa (HSP47\/SERPINH1)","volume":"7","author":"Kumar","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Munteanu, C., Turnea, M.A., and Rotariu, M. (2023). Hydrogen Sulfide: An Emerging Regulator of Oxidative Stress and Cellular Homeostasis\u2014A Comprehensive One-Year Review. Antioxidants, 12.","DOI":"10.3390\/antiox12091737"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"103595","DOI":"10.1016\/j.redox.2025.103595","article-title":"Thiosulphate Sulfurtransferase: Biological Roles and Therapeutic Potential","volume":"82","author":"Luo","year":"2025","journal-title":"Redox Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/s42255-025-01225-w","article-title":"Regulation of Mammalian Cellular Metabolism by Endogenous Cyanide Production","volume":"7","author":"Zuhra","year":"2025","journal-title":"Nat. Metab."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Zeng, T., Jaffar, S., Xu, Y., and Qi, Y. (2022). The Intestinal Immune Defense System in Insects. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232315132"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/7\/881\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T08:38:14Z","timestamp":1784191094000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/7\/881"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,16]]},"references-count":92,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["antiox15070881"],"URL":"https:\/\/doi.org\/10.3390\/antiox15070881","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,16]]}}}