{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:36:08Z","timestamp":1753893368841,"version":"3.41.2"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T00:00:00Z","timestamp":1650844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>We previously reported that the larval <jats:italic>Echinococcus granulosus<\/jats:italic> (<jats:italic>E. granulosus<\/jats:italic>) infection can expand the population of regulatory B cells in mice, thereby inhibiting the anti-infective immunity. However, the underlying mechanism is still largely unknown. This study further investigated the holistic transcriptomic profiles of total splenic B cells following the chronic infection of the parasite.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The infection model of larval <jats:italic>E. granulosus<\/jats:italic> was established by intraperitoneal inoculation with 2000 protoscolexes. Magnetic-Activated Cell Separation (MACS) was used to isolate the total splenic B cells. RNA sequencing was performed to screen the differentially expressed genes (DEGs) after infection. The expression of selected DEGs was verified using qRT-PCR. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Co-expression network analysis were applied to predict these DEGs' underlying biological processes, pathways, and interactions respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 413 DEGs were identified in larval <jats:italic>E. granulosus<\/jats:italic> infected B cells, including 303 up- and 110 down-regulated genes. Notably, most DEGs related to inflammation and chemotaxis were significantly upregulated after infection. In line with these changes, significant expression upregulation of DEGs associated with fatty acid oxidation, lipid synthesis, lipolysis, lipid transport, and cholesterol biosynthesis, were observed in infected B cells. Co-expression network analysis showed an intimate interaction between these DEGs associated with immune and metabolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present study revealed that the larval <jats:italic>E. granulosus<\/jats:italic> infection induces metabolic reprogramming of B cells, which provides a novel clue to clarify the immunoregulatory mechanism of B cells in parasitic infection.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fvets.2022.848458","type":"journal-article","created":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T12:23:43Z","timestamp":1650889423000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Transcriptomic Profiles of Splenic CD19+ B Cells in Mice Chronically Infected With the Larval Echinococcus granulosus"],"prefix":"10.3389","volume":"9","author":[{"given":"Shiping","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxin","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiancheng","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengfei","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyi","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linlin","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zixuan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dingmin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengxiu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoying","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenfen","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1111\/zph.12649","article-title":"Control of cystic echinococcosis: background and prospects","volume":"66","author":"Larrieu","year":"2019","journal-title":"Zoonoses Public Health."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1016\/j.ijpara.2005.07.014","article-title":"Emergence\/re-emergence of Echinococcus spp\u2013a global update","volume":"35","author":"Jenkins","year":"2005","journal-title":"Int J Parasitol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1186\/s13071-017-2263-9","article-title":"The excretory-secretory products of Echinococcus granulosus protoscoleces directly regulate the differentiation of B10, B17 and Th17 cells","volume":"10","author":"Pan","year":"2017","journal-title":"Parasit Vectors."},{"key":"B4","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.mito.2017.11.005","article-title":"Regulation of B cell fate, survival, and function by mitochondria and autophagy","volume":"41","author":"Sandoval","year":"2018","journal-title":"Mitochondrion."},{"key":"B5","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1146\/annurev-immunol-020711-074934","article-title":"Immune regulatory function of B cells","volume":"30","author":"Mauri","year":"2012","journal-title":"Annu Rev Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.immuni.2015.04.005","article-title":"Regulatory B cells: origin, phenotype, and function","volume":"42","author":"Rosser","year":"2015","journal-title":"Immunity."},{"key":"B7","doi-asserted-by":"publisher","first-page":"886","DOI":"10.4049\/jimmunol.0901114","article-title":"Regulatory B cells shape the development of Th2 immune responses in BALB\/c mice infected with Leishmania major through IL-10 production","volume":"184","author":"Ronet","year":"2010","journal-title":"J Immunol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e30883","DOI":"10.1371\/journal.pone.0030883","article-title":"Schistosomes induce regulatory features in human and mouse CD1d(hi) B cells: inhibition of allergic inflammation by IL-10 and regulatory T cells","volume":"7","author":"Van der Vlugt","year":"2012","journal-title":"PLoS One."},{"key":"B9","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1111\/j.1365-2567.2007.02725.x","article-title":"Cordeiro-da-Silva A. A Leishmania infantum cytosolic tryparedoxin activates B cells to secrete interleukin-10 and specific immunoglobulin","volume":"123","author":"Cabral","year":"2008","journal-title":"Immunology."},{"key":"B10","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s12865-018-0267-7","article-title":"The excretory-secretory products of Echinococcus granulosus protoscoleces stimulated IL-10 production in B cells via TLR-2 signaling","volume":"19","author":"Pan","year":"2018","journal-title":"BMC Immunol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1146\/annurev-immunol-032713-120236","article-title":"Metabolic regulation of immune responses","volume":"32","author":"Ganeshan","year":"2014","journal-title":"Annu Rev Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1242454","DOI":"10.1126\/science.1242454","article-title":"Fueling immunity: insights into metabolism and lymphocyte function","volume":"342","author":"Pearce","year":"2013","journal-title":"Science."},{"key":"B13","doi-asserted-by":"publisher","first-page":"4742","DOI":"10.1182\/blood-2009-10-249540","article-title":"Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation","volume":"115","author":"Krawczyk","year":"2010","journal-title":"Blood."},{"key":"B14","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1038\/nature11986","article-title":"Succinate is an inflammatory signal that induces IL-1\u03b2 through HIF-1\u03b1","volume":"496","author":"Tannahill","year":"2013","journal-title":"Nature."},{"key":"B15","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/S0021-9258(18)88742-7","article-title":"The action of leucocytes on glucose","volume":"11","author":"Levene P","year":"1912","journal-title":"J Biol Chem."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1038\/nm.3704","article-title":"De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells","volume":"20","author":"Berod","year":"2014","journal-title":"Nat Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"3190","DOI":"10.4049\/jimmunol.1302985","article-title":"Regulator of fatty acid metabolism, acetyl coenzyme a carboxylase 1, controls T cell immunity","volume":"192","author":"Lee","year":"2014","journal-title":"J Immunol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"425","DOI":"10.4049\/jimmunol.1601908","article-title":"Metabolic reprogramming commits differentiation of human CD27+IgD+ B cells to plasmablasts or CD27\u2212IgD\u2212 cells","volume":"199","author":"Torigoe","year":"2017","journal-title":"J Immunol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1017\/S0031182004005670","article-title":"Characterization of excretory-secretory products from protoscoleces of Echinococcus granulosus and evaluation of their potential for immunodiagnosis of human cystic echinococcosis","volume":"129","author":"Carmena","year":"2004","journal-title":"Parasitology."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e59746","DOI":"10.1371\/journal.pone.0059746","article-title":"Surveillance on the status of immune cells after Echinnococcus granulosus protoscoleces infection in Balb\/c mice","volume":"8","author":"Pan","year":"2013","journal-title":"PLoS ONE."},{"key":"B21","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat Methods."},{"key":"B22","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: a fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat Methods."},{"key":"B23","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1186\/1471-2105-12-323","article-title":"RSEM accurate transcript quantification from RNA-Seq data with or without a reference genome","volume":"12","author":"Li","year":"2011","journal-title":"BMC Bioinformatics."},{"key":"B24","doi-asserted-by":"publisher","first-page":"3362","DOI":"10.1016\/j.febslet.2015.08.048","article-title":"The regulatory role of B cells in autoimmunity, infections and cancer: perspectives beyond IL10 production","volume":"589","author":"Gorosito Serr\u00e1n","year":"2015","journal-title":"FEBS Lett."},{"key":"B25","doi-asserted-by":"publisher","first-page":"718743","DOI":"10.3389\/fvets.2021.718743","article-title":"Metabolomics analysis of splenic CD19+ B Cells in mice chronically infected with Echinococcus granulosus sensu lato Protoscoleces","volume":"8","author":"Guo","year":"2021","journal-title":"Front Vet Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1089\/jir.2014.0026","article-title":"The role of cytokines in breast cancer development and progression","volume":"35","author":"Esquivel-Vel\u00e1zquez","year":"2015","journal-title":"J Interferon Cytokine Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1007\/s10753-020-01254-5","article-title":"MiRNA-495-3p Attenuates TNF-\u03b1 Induced Apoptosis and Inflammation in Human Nucleus Pulposus Cells by Targeting IL5RA","volume":"43","author":"Lin","year":"2020","journal-title":"Inflammation."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.imlet.2018.11.003","article-title":"Cross-talk between signal transduction and metabolism in B cells","volume":"201","author":"Jellusova","year":"2018","journal-title":"Immunol Lett."},{"key":"B29","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1007\/978-981-16-0267-2","article-title":"Lipid metabolism and immune checkpoints","volume":"1316","author":"Liao","year":"2021","journal-title":"Adv Exp Med Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/s41392-020-0117-y","article-title":"The Agpat4\/LPA axis in colorectal cancer cells regulates antitumor responses via p38\/p65 signaling in macrophages","volume":"5","author":"Zhang","year":"2020","journal-title":"Signal Transduct Target Ther."},{"key":"B31","doi-asserted-by":"publisher","first-page":"639362","DOI":"10.1155\/2012\/639362","article-title":"Host-parasite relationship in cystic echinococcosis: an evolving story","volume":"2012","author":"Siracusano","year":"2012","journal-title":"Clin Dev Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1038\/ni.2569","article-title":"Trypanosoma cruzi trans-sialidase initiates a program independent of the transcription factors ROR\u03b3t and Ahr that leads to IL-17 production by activated B cells","volume":"14","author":"Bermejo","year":"2013","journal-title":"Nat Immunol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1038\/nri.2016.70","article-title":"A guide to immunometabolism for immunologists","volume":"16","author":"O'Neill","year":"2016","journal-title":"Nat Rev Immunol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"7817","DOI":"10.1073\/pnas.0912059107","article-title":"Induction of fatty acid synthesis is a key requirement for phagocytic differentiation of human monocytes","volume":"107","author":"Ecker","year":"2010","journal-title":"Proc Natl Acad Sci USA."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1016\/j.cell.2015.10.068","article-title":"CD5L\/AIM regulates lipid biosynthesis and restrains Th17 cell pathogenicity","volume":"163","author":"Wang","year":"2015","journal-title":"Cell."},{"key":"B36","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1097\/COH.0b013e328335c2f6","article-title":"Th17 cytokines in mucosal immunity and inflammation","volume":"5","author":"Guglani","year":"2010","journal-title":"Curr Opin HIV AIDS."},{"key":"B37","doi-asserted-by":"publisher","first-page":"7011","DOI":"10.1074\/jbc.M114.551051","article-title":"Glucose-dependent de novo lipogenesis in B lymphocytes: a requirement for atp-citrate lyase in lipopolysaccharide-induced differentiation","volume":"289","author":"Dufort","year":"2014","journal-title":"J Biol Chem."},{"key":"B38","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/s41590-020-0598-4","article-title":"Germinal center B cells selectively oxidize fatty acids for energy while conducting minimal glycolysis","volume":"21","author":"Weisel","year":"2020","journal-title":"Nat Immunol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"3412","DOI":"10.1038\/s41467-020-17179-4","article-title":"Cholesterol metabolism drives regulatory B cell IL-10 through provision of geranylgeranyl pyrophosphate","volume":"11","author":"Bibby","year":"2020","journal-title":"Nat Commun."},{"key":"B40","doi-asserted-by":"publisher","first-page":"18","DOI":"10.3389\/fcvm.2019.00018","article-title":"Autotaxin and lipoprotein metabolism in calcific aortic valve disease","volume":"6","author":"Mathieu","year":"2019","journal-title":"Front Cardiovasc Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"2371","DOI":"10.1002\/oby.21232","article-title":"Serum Autotaxin\/ENPP2 correlates with insulin resistance in older humans with obesity","volume":"23","author":"Reeves","year":"2015","journal-title":"Obesity (Silver Spring)."},{"key":"B42","doi-asserted-by":"publisher","first-page":"e136283","DOI":"10.1172\/jci.insight.136283","article-title":"GPx3 dysregulation impacts adipose tissue insulin receptor expression and sensitivity","volume":"5","author":"Hauffe","year":"2020","journal-title":"JCI Insight."},{"key":"B43","doi-asserted-by":"publisher","first-page":"2176","DOI":"10.1210\/me.2008-0023","article-title":"Dysregulation of adipose glutathione peroxidase 3 in obesity contributes to local and systemic oxidative stress","volume":"22","author":"Lee","year":"2008","journal-title":"Mol Endocrinol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/nri1056","article-title":"PI3K in lymphocyte development, differentiation and activation","volume":"3","author":"Okkenhaug","year":"2003","journal-title":"Nat Rev Immunol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1038\/s41598-018-19460-5","article-title":"PI3K induces B-cell development and regulates B cell identity","volume":"8","author":"Abdelrasoul","year":"2018","journal-title":"Sci Rep."},{"key":"B46","doi-asserted-by":"publisher","first-page":"3702","DOI":"10.1172\/JCI93820","article-title":"Microbiota maintain colonic homeostasis by activating TLR2\/MyD88\/PI3K signaling in IL-10-producing regulatory B cells","volume":"129","author":"Mishima","year":"2019","journal-title":"J Clin Invest."},{"key":"B47","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1111\/j.1600-065X.2010.00934.x","article-title":"Role of PI3K in the generation and survival of B cells","volume":"237","author":"Werner","year":"2010","journal-title":"Immunol Rev."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.2174\/1381612824666180327165604","article-title":"Signaling pathways in inflammation and anti-inflammatory therapies","volume":"24","author":"Yeung","year":"2018","journal-title":"Curr Pharm Des."},{"key":"B49","doi-asserted-by":"publisher","first-page":"2548","DOI":"10.1038\/sj.onc.1203551","article-title":"Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors","volume":"19","author":"Hirano","year":"2000","journal-title":"Oncogene."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1016\/j.molimm.2009.02.018","article-title":"STAT3 tyrosine phosphorylation is critical for interleukin 1 beta and interleukin-6 production in response to lipopolysaccharide and live bacteria","volume":"46","author":"Samavati","year":"2009","journal-title":"Mol Immunol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"16975","DOI":"10.1073\/pnas.1315862110","article-title":"STAT3 activation in response to IL-6 is prolonged by the binding of IL-6 receptor to EGF receptor","volume":"110","author":"Wang","year":"2013","journal-title":"Proc Natl Acad Sci U S A."},{"key":"B52","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.cmet.2018.04.018","article-title":"JAK\/STAT3-regulated fatty acid \u03b2-oxidation is critical for breast cancer stem cell self-renewal and chemoresistance","volume":"27","author":"Wang","year":"2018","journal-title":"Cell Metab"},{"key":"B53","doi-asserted-by":"publisher","first-page":"487","DOI":"10.2174\/1389450117666161207163054","article-title":"JAK\/STAT signal transduction: promising attractive targets for immune, inflammatory and hematopoietic diseases","volume":"19","author":"Gao","year":"2018","journal-title":"Curr Drug Targets."},{"key":"B54","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1002\/path.1437","article-title":"Functional structure and composition of the extracellular matrix","volume":"200","author":"Bosman","year":"2003","journal-title":"J Pathol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1126\/science.1176009","article-title":"The extracellular matrix: not just pretty fibrils","volume":"326","author":"Hynes","year":"2009","journal-title":"Science."},{"key":"B56","doi-asserted-by":"publisher","first-page":"105886","DOI":"10.1016\/j.actatropica.2021.105886","article-title":"In vitro immunoregulatory activity and anti-inflammatory effect of Echinococcus granulosus laminated layer","volume":"218","author":"Benazzouz","year":"2021","journal-title":"Acta Trop."},{"key":"B57","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1016\/j.jiph.2018.06.007","article-title":"Th1\/Th2-type cytokine profile in C57 black mice inoculated with live Echinococcus granulosus protoscolices","volume":"11","author":"Rostami-Rad","year":"2018","journal-title":"J Infect Public Health."}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2022.848458\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T12:23:45Z","timestamp":1650889425000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2022.848458\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,25]]},"references-count":57,"alternative-id":["10.3389\/fvets.2022.848458"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2022.848458","relation":{},"ISSN":["2297-1769"],"issn-type":[{"type":"electronic","value":"2297-1769"}],"subject":[],"published":{"date-parts":[[2022,4,25]]},"article-number":"848458"}}