{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T04:48:40Z","timestamp":1781153320024,"version":"3.54.1"},"reference-count":92,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T00:00:00Z","timestamp":1748044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health, National Institute of Allergy and Infectious Diseases","award":["AI056273"],"award-info":[{"award-number":["AI056273"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Schistosomes are intravascular parasitic worms that cause the debilitating tropical disease schistosomiasis, affecting &gt;200 million people worldwide. How the worms survive within the body of immunocompetent hosts for many years is unclear. Here, using chromatography and mass spectrometry, we report on the ex vivo ability of adult Schistosoma mansoni worms to modulate the levels of 27 small molecule (often immunomodulatory) metabokines in murine plasma. Schistosomes significantly alter the relative amounts of most (16) of these molecules. Three (inosine, genistein, and glucose) are significantly decreased in the presence of the parasites. While levels of several immunomodulatory metabolites from the kynurenine pathway (kynurenine, kynurenic acid, and xanthurenic acid) remain unchanged, levels of anthranilate (an endogenous regulator of innate immunity) are significantly increased. Of particular interest are increases in levels of metabolites that are known to skew immune responses in a manner that is seen following natural schistosome infection, such as by promoting Th2 immunity (succinate), Treg generation (lactate) and M2 macrophage polarization (lactate and succinate). In addition, significant increases are also observed for 2-hydroxyglutarate, adenine, hypoxanthine, xanthine, myoinositol, betaine and N-acetylglucosamine. Each of these compounds can have immunosuppressive effects that could impact host immunological status and contribute to schistosome survival.<\/jats:p>","DOI":"10.3390\/pathogens14060526","type":"journal-article","created":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T20:26:50Z","timestamp":1748204810000},"page":"526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Generation of Immune Modulating Small Metabolites\u2014Metabokines\u2014By Adult Schistosomes"],"prefix":"10.3390","volume":"14","author":[{"given":"Patrick J.","family":"Skelly","sequence":"first","affiliation":[{"name":"Molecular Helminthology Laboratory, Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3318-9623","authenticated-orcid":false,"given":"Akram A.","family":"Da\u2019dara","sequence":"additional","affiliation":[{"name":"Molecular Helminthology Laboratory, Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/scientificamerican0508-94","article-title":"Fighting killer worms","volume":"298","author":"Skelly","year":"2008","journal-title":"Sci. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1016\/S0140-6736(13)61949-2","article-title":"Human schistosomiasis","volume":"383","author":"Colley","year":"2014","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Acharya, S., Da\u2019dara, A.A., and Skelly, P.J. (2021). Schistosome immunomodulators. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1010064"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1016\/j.pt.2022.09.001","article-title":"Schistosoma mansoni and the purinergic halo","volume":"38","author":"Skelly","year":"2022","journal-title":"Trends Parasitol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"106676","DOI":"10.1016\/j.actatropica.2022.106676","article-title":"Schistosome secretomes","volume":"236","author":"Skelly","year":"2022","journal-title":"Acta Trop."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.molcel.2020.04.002","article-title":"Cytokine-like Roles for Metabolites in Immunity","volume":"78","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Morrot, A., Da Fonseca, L.M., Salustiano, E.J., Gentile, L.B., Conde, L., Filardy, A.A., Franklim, T.N., da Costa, K.M., Freire-De-Lima, C.G., and Freire-De-Lima, L. (2018). Metabolic Symbiosis and Immunomodulation: How Tumor Cell-Derived Lactate May Disturb Innate and Adaptive Immune Responses. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00081"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Weiss, H.J., and Angiari, S. (2020). Metabolite Transporters as Regulators of Immunity. Metabolites, 10.","DOI":"10.3390\/metabo10100418"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Errea, A., Cayet, D., Marchetti, P., Tang, C., Kluza, J., Offermanns, S., Sirard, J.-C., and Rumbo, M. (2016). Lactate Inhibits the Pro-Inflammatory Response and Metabolic Reprogramming in Murine Macrophages in a GPR81-Independent Manner. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0163694"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1073\/pnas.1614035114","article-title":"Gpr132 sensing of lactate mediates tumor-macrophage interplay to promote breast cancer metastasis","volume":"114","author":"Chen","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.tcb.2013.11.008","article-title":"Succinate: A metabolic signal in inflammation","volume":"24","author":"Mills","year":"2014","journal-title":"Trends Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/cei.12591","article-title":"Citrate modulates lipopolysaccharide-induced monocyte inflammatory responses","volume":"180","author":"Ashbrook","year":"2015","journal-title":"Clin. Exp. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1177\/1352458520937282","article-title":"Dimethyl fumarate treatment shifts the immune environment toward an anti-inflammatory cell profile while maintaining protective humoral immunity","volume":"27","author":"Cascione","year":"2021","journal-title":"Mult. Scler."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Tanaka, M., T\u00f3th, F., Poly\u00e1k, H., Szab\u00f3, \u00c1., M\u00e1ndi, Y., and V\u00e9csei, L. (2021). Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway. Biomedicines, 9.","DOI":"10.20944\/preprints202106.0344.v1"},{"key":"ref_15","first-page":"19.1.1","article-title":"Schistosomiasis","volume":"103","author":"Tucker","year":"2013","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Elzoheiry, M., Da\u2019dara, A.A., Bhardwaj, R., Wang, Q., Azab, M.S., El-Kholy, E.-S.I., El-Beshbishi, S.N., and Skelly, P.J. (2018). Intravascular Schistosoma mansoni Cleave the Host Immune and Hemostatic Signaling Molecule Sphingosine-1-Phosphate via Tegumental Alkaline Phosphatase. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01746"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6656","DOI":"10.1021\/ac901536h","article-title":"Integrated, nontargeted ultrahigh performance liquid chromatography\/electrospray ionization tandem mass spectrometry platform for the identification and relative quantification of the small-molecule complement of biological systems","volume":"81","author":"Evans","year":"2009","journal-title":"Anal. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"114676","DOI":"10.1016\/j.intimp.2025.114676","article-title":"L-Kynurenine regulates immune response in ICIs-associated myocarditis via JAK\/STAT pathway","volume":"156","author":"He","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Krautz-Peterson, G., Simoes, M., Faghiri, Z., Ndegwa, D., Oliveira, G., Shoemaker, C.B., and Skelly, P.J. (2010). Suppressing glucose transporter gene expression in schistosomes impairs parasite feeding and decreases survival in the mammalian host. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000932"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4247","DOI":"10.1016\/S0021-9258(17)41770-4","article-title":"Cloning, characterization and functional expression of cDNAs encoding glucose transporter proteins from the human parasite, Schistosoma mansoni","volume":"269","author":"Skelly","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1085\/jgp.33.5.475","article-title":"Carbohydrate metabolism of Schistosoma mansoni","volume":"33","author":"Bueding","year":"1950","journal-title":"J. Gen. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"385","DOI":"10.2307\/3279308","article-title":"Aerobic and anaerobic carbohydrate metabolism and egg production of Schistosoma mansoni in vitro","volume":"61","author":"Schiller","year":"1975","journal-title":"J. Parasitol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Faghiri, Z., Camargo, S.M.R., Huggel, K., Forster, I.C., Ndegwa, D., Verrey, F., and Skelly, P.J. (2010). The tegument of the human parasitic worm Schistosoma mansoni as an excretory organ: The surface aquaporin SmAQP is a lactate transporter. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010451"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Iraporda, C., Romanin, D.E., Bengoa, A.A., Errea, A.J., Cayet, D., Folign\u00e9, B., Sirard, J.-C., Garrote, G.L., Abraham, A.G., and Rumbo, M. (2016). Local Treatment with Lactate Prevents Intestinal Inflammation in the TNBS-Induced Colitis Model. Front. Immunol., 7.","DOI":"10.3389\/fimmu.2016.00651"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1080\/08830185.2021.1974856","article-title":"Effects of lactate in immunosuppression and inflammation: Progress and prospects","volume":"41","author":"Luo","year":"2022","journal-title":"Int. Rev. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Manoharan, I., Prasad, P.D., Thangaraju, M., and Manicassamy, S. (2021). Lactate-Dependent Regulation of Immune Responses by Dendritic Cells and Macrophages. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.691134"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wang, Z., Dai, Z., Zhang, H., Liang, X., Zhang, X., Wen, Z., Luo, P., Zhang, J., Liu, Z., and Zhang, M. (2023). Tumor-secreted lactate contributes to an immunosuppressive microenvironment and affects CD8 T-cell infiltration in glioblastoma. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.894853"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3681","DOI":"10.1038\/s41388-019-0688-7","article-title":"Lactate modulates CD4(+) T-cell polarization and induces an immunosuppressive environment, which sustains prostate carcinoma progression via TLR8\/miR21 axis","volume":"38","author":"Comito","year":"2019","journal-title":"Oncogene"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"103918","DOI":"10.1016\/j.cellimm.2019.04.006","article-title":"Lactic acid suppresses IgE-mediated mast cell function in vitro and in vivo","volume":"341","author":"Abebayehu","year":"2019","journal-title":"Cell Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Farsani, S.S.M., and Verma, V. (2023). Lactate mediated metabolic crosstalk between cancer and immune cells and its therapeutic implications. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1175532"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zhang, T., Chen, L., Kueth, G., Shao, E., Wang, X., Ha, T., Williams, D.L., Li, C., Fan, M., and Yang, K. (2024). Lactate\u2019s impact on immune cells in sepsis: Unraveling the complex interplay. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1483400"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/imm.13231","article-title":"Schistosome and intestinal helminth modulation of macrophage immunometabolism","volume":"162","author":"Fairfax","year":"2021","journal-title":"Immunology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1080\/15384101.2018.1444305","article-title":"Tumor-derived lactate induces M2 macrophage polarization via the activation of the ERK\/STAT3 signaling pathway in breast cancer","volume":"17","author":"Mu","year":"2018","journal-title":"Cell Cycle"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e2102434118","DOI":"10.1073\/pnas.2102434118","article-title":"The macrophage odorant receptor Olfr78 mediates the lactate-induced M2 phenotype of tumor-associated macrophages","volume":"118","author":"Vadevoo","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nature13490","article-title":"Functional polarization of tumour-associated macrophages by tumour-derived lactic acid","volume":"513","author":"Colegio","year":"2014","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.7150\/ijbs.7.1412","article-title":"Mechanisms underlying the induction of regulatory T cells and its relevance in the adaptive immune response in parasitic infections","volume":"7","author":"Fragoso","year":"2011","journal-title":"Int. J. Biol. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0166-6851(93)90032-S","article-title":"Expression of Schistosoma mansoni genes involved in anaerobic and oxidative glucose metabolism during the cercaria to adult transformation","volume":"60","author":"Skelly","year":"1993","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.7150\/ijbs.91109","article-title":"Exogenous alpha-ketoglutarate Modulates Redox Metabolism and Functions of Human Dendritic Cells, Altering Their Capacity to Polarise T Cell Response","volume":"20","year":"2024","journal-title":"Int. J. Biol. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"skad213","DOI":"10.1093\/jas\/skad213","article-title":"Dietary alpha-ketoglutarate enhances intestinal immunity by Th17\/Treg immune response in piglets after lipopolysaccharide challenge","volume":"101","author":"Liu","year":"2023","journal-title":"J. Anim. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"577230","DOI":"10.1016\/j.jneuroim.2020.577230","article-title":"Dimethyl fumarate promotes B cell-mediated anti-inflammatory cytokine profile in B and T cells, and inhibits immune cell migration in patients with MS","volume":"343","author":"Najjar","year":"2020","journal-title":"J. Neuroimmunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1615\/CritRevImmunol.2013007247","article-title":"Dimethyl fumarate modulation of immune and antioxidant responses: Application to HIV therapy","volume":"33","author":"Gill","year":"2013","journal-title":"Crit. Rev. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.stem.2018.01.020","article-title":"Macrophage-Derived Extracellular Succinate Licenses Neural Stem Cells to Suppress Chronic Neuroinflammation","volume":"22","author":"Bernstock","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Huang, H., Li, G., He, Y., Chen, J., Yan, J., Zhang, Q., Li, L., and Cai, X. (2024). Cellular succinate metabolism and signaling in inflammation: Implications for therapeutic intervention. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1404441"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.immuni.2018.06.016","article-title":"Detection of Succinate by Intestinal Tuft Cells Triggers a Type 2 Innate Immune Circuit","volume":"49","author":"Nadjsombati","year":"2018","journal-title":"Immunity"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2190300","DOI":"10.1080\/19490976.2023.2190300","article-title":"Succinate metabolism and its regulation of host-microbe interactions","volume":"15","author":"Wei","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8","DOI":"10.5217\/ir.2023.00059","article-title":"Helminths in alternative therapeutics of inflammatory bowel disease","volume":"23","author":"Pandey","year":"2025","journal-title":"Intest. Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mickael, C.S., and Graham, B.B. (2019). The Role of Type 2 Inflammation in Schistosoma-Induced Pulmonary Hypertension. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00027"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1186\/s12974-023-02998-1","article-title":"Succinate-induced macrophage polarization and RBP4 secretion promote vascular sprouting in ocular neovascularization","volume":"20","author":"Shen","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.molcel.2019.10.023","article-title":"Cancer-Derived Succinate Promotes Macrophage Polarization and Cancer Metastasis via Succinate Receptor","volume":"77","author":"Wu","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Zhang, W., and Lang, R. (2023). Succinate metabolism: A promising therapeutic target for inflammation, ischemia\/reperfusion injury and cancer. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1266973"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.cmet.2020.07.016","article-title":"The Immunomodulatory Metabolite Itaconate Modifies NLRP3 and Inhibits Inflammasome Activation","volume":"32","author":"Hooftman","year":"2020","journal-title":"Cell Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1007\/s10753-023-01819-0","article-title":"Itaconate: A Potent Macrophage Immunomodulator","volume":"46","author":"Li","year":"2023","journal-title":"Inflammation"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"de Goede, K.E., Harber, K.J., Gorki, F.S., Verberk, S.G., Groh, L.A., Keuning, E.D., Struys, E.A., van Weeghel, M., Haschemi, A., and de Winther, M.P. (2022). d-2-Hydroxyglutarate is an anti-inflammatory immunometabolite that accumulates in macrophages after TLR4 activation. Biochim. Biophys. Acta (BBA)\u2014Mol. Basis Dis., 1868.","DOI":"10.1016\/j.bbadis.2022.166427"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e24454","DOI":"10.1016\/j.heliyon.2024.e24454","article-title":"Oncometabolite 2-hydroxyglutarate regulates anti-tumor immunity","volume":"10","author":"Cai","year":"2024","journal-title":"Heliyon"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1126\/science.abj5104","article-title":"Oncometabolite d-2HG alters T cell metabolism to impair CD8(+) T cell function","volume":"377","author":"Notarangelo","year":"2022","journal-title":"Science"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1177\/00045632241297873","article-title":"Usefulness of the 3-hydroxykynurenine\/kynurenic acid ratio as a diagnostic biomarker for diffuse larger B-cell lymphoma","volume":"62","author":"Yamamoto","year":"2025","journal-title":"Ann. Clin. Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2244330","DOI":"10.1080\/2162402X.2023.2244330","article-title":"L-Kynurenine participates in cancer immune evasion by downregulating hypoxic signaling in T lymphocytes","volume":"12","author":"Schlichtner","year":"2023","journal-title":"Oncoimmunology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"19961","DOI":"10.1073\/pnas.1014465107","article-title":"Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism","volume":"107","author":"Nguyen","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1021\/acschemneuro.1c00818","article-title":"Anti-Inflammatory Anthranilate Analogue Enhances Autophagy through mTOR and Promotes ER-Turnover through TEX264 during Alzheimer-Associated Neuroinflammation","volume":"13","author":"Wang","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6783","DOI":"10.1096\/fj.201800354","article-title":"Topical application of anthranilate derivatives ameliorates psoriatic inflammation in a mouse model by inhibiting keratinocyte-derived chemokine expression and neutrophil infiltration","volume":"32","author":"Lin","year":"2018","journal-title":"FASEB J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e316","DOI":"10.7717\/peerj.316","article-title":"Schistosome tegumental ecto-apyrase (SmATPDase1) degrades exogenous pro-inflammatory and pro-thrombotic nucleotides","volume":"2","author":"Bhardwaj","year":"2014","journal-title":"PeerJ"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1055\/s-0038-1641715","article-title":"The Essential Ectoenzyme SmNPP5 from the Human Intravascular Parasite Schistosoma mansoni is an ADPase and a Potent Inhibitor of Platelet Aggregation","volume":"118","author":"Elzoheiry","year":"2018","journal-title":"Thromb. Haemost."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1080\/21505594.2020.1770481","article-title":"The essential schistosome tegumental ectoenzyme SmNPP5 can block NAD-induced T cell apoptosis","volume":"11","author":"Nation","year":"2020","journal-title":"Virulence"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1042\/BCJ20210784","article-title":"NAD-catabolizing ectoenzymes of Schistosoma mansoni","volume":"479","author":"Nation","year":"2022","journal-title":"Biochem. J."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Bhardwaj, R., and Skelly, P.J. (2011). Characterization of schistosome tegumental alkaline phosphatase (SmAP). PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001011"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Zahavi, D., and Hodge, J.W. (2023). Targeting Immunosuppressive Adenosine Signaling: A Review of Potential Immunotherapy Combination Strategies. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24108871"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Pasquini, S., Contri, C., Borea, P.A., Vincenzi, F., and Varani, K. (2021). Adenosine and Inflammation: Here, There and Everywhere. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147685"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1007\/s00210-016-1264-0","article-title":"Adenine attenuates the Ca(2+) contraction-signaling pathway via adenine receptor-mediated signaling in rat vascular smooth muscle cells","volume":"389","author":"Fukuda","year":"2016","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.imlet.2023.12.003","article-title":"Adenine is an anti-inflammatory metabolite found to be more abundant in M-CSF over GM-CSF-differentiated human macrophages","volume":"265","author":"Harber","year":"2024","journal-title":"Immunol. Lett."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/0006-2952(73)90285-2","article-title":"Pathways of nucleotide metabolism in Schistosoma mansoni. II. Disposition of adenosine by whole worms","volume":"22","author":"Senft","year":"1973","journal-title":"Biochem. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Gao, L., Zhang, Y., Hu, Z., Chen, S., Wang, Q., Zeng, Y., Yin, H., Zhao, J., Zhan, Y., and Gao, C. (2025). Microbiota-Derived Inosine Suppresses Systemic Autoimmunity via Restriction of B Cell Differentiation and Migration. Adv. Sci., e2409837.","DOI":"10.1002\/advs.202409837"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.tips.2004.01.006","article-title":"Immunomodulatory and neuroprotective effects of inosine","volume":"25","author":"Sitkovsky","year":"2004","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/BF02981908","article-title":"New clinical applications of xanthine derivatives: Modulatory actions on leukocyte survival and function","volume":"73","author":"Yasui","year":"2001","journal-title":"Int. J. Hematol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Baldassarre, M.P.A., Di Tomo, P., Centorame, G., Pandolfi, A., Di Pietro, N., Consoli, A., and Formoso, G. (2021). Myoinositol Reduces Inflammation and Oxidative Stress in Human Endothelial Cells Exposed In Vivo to Chronic Hyperglycemia. Nutrients, 13.","DOI":"10.3390\/nu13072210"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.ibneur.2024.01.009","article-title":"Long-term effects of myo-inositol on traumatic brain injury: Epigenomic and transcriptomic studies","volume":"16","author":"Oganezovi","year":"2024","journal-title":"IBRO Neurosci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Zhao, G., He, F., Wu, C., Li, P., Li, N., Deng, J., Zhu, G., Ren, W., and Peng, Y. (2018). Betaine in Inflammation: Mechanistic Aspects and Applications. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01070"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"657","DOI":"10.3109\/02713683.2014.957776","article-title":"Effects of L-carnitine, erythritol and betaine on pro-inflammatory markers in primary human corneal epithelial cells exposed to hyperosmotic stress","volume":"40","author":"Hua","year":"2015","journal-title":"Curr. Eye Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"40133","DOI":"10.1074\/jbc.M111.277814","article-title":"N-acetylglucosamine inhibits T-helper 1 (Th1)\/T-helper 17 (Th17) cell responses and treats experimental autoimmune encephalomyelitis","volume":"286","author":"Grigorian","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Marchetti, M., De Berardis, B., Bigioni, I., Mariano, A., Superti, F., and D\u2019abusco, A.S. (2023). In Vitro Antiviral and Anti-Inflammatory Activities of N-Acetylglucosamine: Development of an Alternative and Safe Approach to Fight Viral Respiratory Infections. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065129"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1002\/ptr.6573","article-title":"A review on gentisic acid as a plant derived phenolic acid and metabolite of aspirin: Comprehensive pharmacology, toxicology, and some pharmaceutical aspects","volume":"34","author":"Abedi","year":"2020","journal-title":"Phytother. Res."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Guo, X. (2023). Antibacterial and anti-inflammatory effects of genistein in Staphylococcus aureus induced osteomyelitis in rats. J. Biochem. Mol. Toxicol., 37.","DOI":"10.1002\/jbt.23298"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Goh, Y.X., Jalil, J., Lam, K.W., Husain, K., and Premakumar, C.M. (2022). Genistein: A Review on its Anti-Inflammatory Properties. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.820969"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1177\/135965350400900419","article-title":"Activation of dendritic cells and induction of T cell responses by HPV 16 L1\/E7 chimeric virus-like particles are enhanced by CpG ODN or sorbitol","volume":"9","author":"Freyschmidt","year":"2004","journal-title":"Antivir. Ther."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1111\/j.1600-0625.2010.01107.x","article-title":"Azelaic acid modulates the inflammatory response in normal human keratinocytes through PPARgamma activation","volume":"19","author":"Mastrofrancesco","year":"2010","journal-title":"Exp. Dermatol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1038\/s41467-021-21461-4","article-title":"Fructose reprogrammes glutamine-dependent oxidative metabolism to support LPS-induced inflammation","volume":"12","author":"Jones","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"298","DOI":"10.4103\/ccd.ccd_53_18","article-title":"The Anti-inflammatory Effects of Glycerol-supplemented Probiotic Lactobacillus reuteri on Infected Epithelial cells In vitro","volume":"9","author":"Widyarman","year":"2018","journal-title":"Contemp. Clin. Dent."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1111\/jdv.13225","article-title":"Anti-irritant and anti-inflammatory effects of glycerol and xylitol in sodium lauryl sulphate-induced acute irritation","volume":"29","author":"Hartmann","year":"2015","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.pt.2019.01.012","article-title":"Twenty Years on: Metabolomics in Helminth Research","volume":"35","author":"Kokova","year":"2019","journal-title":"Trends Parasitol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Adebayo, A.S., Mundhe, S.D., Awobode, H.O., Onile, O.S., Agunloye, A.M., Isokpehi, R.D., Shouche, Y.S., Santhakumari, B., and Anumudu, C.I. (2018). Metabolite profiling for biomarkers in Schistosoma haematobium infection and associated bladder pathologies. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006452"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/s42255-024-00981-5","article-title":"Monocarboxylate transporters facilitate succinate uptake into brown adipocytes","volume":"6","author":"Reddy","year":"2024","journal-title":"Nat. Metab."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1097\/01.ana.0000211002.63774.8a","article-title":"Increased lactate levels impair the coagulation system\u2014A potential contributing factor to progressive hemorrhage after traumatic brain injury","volume":"18","author":"Engstrom","year":"2006","journal-title":"J. Neurosurg. Anesth."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.thromres.2019.03.011","article-title":"Higher lactate and purine metabolite levels in erythrocyte-rich fresh venous thrombus: Potential markers for early deep vein thrombosis","volume":"177","author":"Maekawa","year":"2019","journal-title":"Thromb. Res."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/6\/526\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:39:50Z","timestamp":1760031590000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/6\/526"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,24]]},"references-count":92,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["pathogens14060526"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14060526","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,24]]}}}