{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T05:01:11Z","timestamp":1780290071698,"version":"3.54.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      It is documented that\n                      <jats:italic>Schistosoma mansoni<\/jats:italic>\n                      antigens can induce immune responses able to regulate complex diseases. Conversely, the dysregulated inflammatory response in leprosy increases morbidity and leads to reactional episodes, impairing the disease pathogenesis. The goal of this study was to evaluate the potential of the\n                      <jats:italic>S. mansoni<\/jats:italic>\n                      (Sm29) antigen in regulating the immune response in leprosy through a transcriptome study across clinical reactional forms: reversal reaction (RR), and erythema nodosum leprosum (ENL), and without reaction (WR).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Peripheral blood mononuclear cells (PBMCs) were cultured and stimulated with sonicated\n                      <jats:italic>M. leprae<\/jats:italic>\n                      antigen and rSm29 antigen. Total RNA was extracted by the TRIzol\n                      <jats:sup>\u00ae<\/jats:sup>\n                      (Ambion) according to the manufacturer\u2019s protocol. RNA libraries were constructed with the TruSeq Stranded Total RNA Prep Globin kit (Illumina) and quantified by qPCR with the KAPA Library Quantification Kit (Roche). Sequencing was performed by Nextseq 2000 (Illumina) with 2x100 base pairs (bp) reads. Differential expression was analyzed using DESeq2 to identify differentially expressed genes (DEGs) between conditions. Identified DEGS were subjected to Ingenuity Pathway Analysis (IPA)for enrichment pathway analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The Sm29 antigen was able to modulate immune response pathways in leprosy, with this response being more pronounced in the reactional forms of the disease, especially in RR. Interestingly, when compared to sonicated\n                      <jats:italic>M. leprae<\/jats:italic>\n                      , Sm29 had an opposite effect in RR-ENL, evidenced by the top genes most expressed in RR and less in the ENL (\n                      <jats:italic>C2CD4B, CEMIP, IL23A, CD7, GPC5, EBF1, SIGLEC15, ADAT2, ZC3H12D<\/jats:italic>\n                      ); Additionally, IPA analysis shown that in RR, modulation of the\n                      <jats:italic>CSF2<\/jats:italic>\n                      by Sm29 increases\n                      <jats:italic>IL10<\/jats:italic>\n                      , while modulation by IFN-\u03b1 modulates\n                      <jats:italic>CXCL9, CXCL-10, IL15, TLRs 2<\/jats:italic>\n                      and\n                      <jats:italic>4<\/jats:italic>\n                      ; On the other hand, in ENL, modulation of\n                      <jats:italic>IL1B<\/jats:italic>\n                      and\n                      <jats:italic>FN1<\/jats:italic>\n                      genes by rSm29 appear related to several chemokines and cytokines such as\n                      <jats:italic>IL6, CCL2<\/jats:italic>\n                      and\n                      <jats:italic>CXCL8<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Leprosy proves to be an efficient model for investigating products capable of regulating the host inflammatory response. Here, we open perspectives for new insights in the use of immunobiological, expanding attention to this field that might help management of leprosy patients, especially in reactional episodes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1844112","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T04:18:55Z","timestamp":1780287535000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The Sm29 antigen differentially shapes transcriptomic and regulatory landscapes across reactional forms of leprosy"],"prefix":"10.3389","volume":"17","author":[{"given":"Joyce","family":"Karoline Silva","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade da Universidade Federal da Bahia","place":["Salvador, Brazil"]},{"name":"Laborat\u00f3rio de Medicina e Sa\u00fade P\u00fablica de Precis\u00e3o \u2013 MESP\u00b2 \u2013 Instituto Gon\u00e7alo Moniz-FIOCRUZ","place":["Bahia, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Neves","family":"de Farias","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade da Universidade Federal da Bahia","place":["Salvador, Brazil"]},{"name":"Servi\u00e7o de Imunologia da Universidade Federal da Bahia","place":["Salvador, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tain\u00e3","family":"Lago","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade da Universidade Federal da Bahia","place":["Salvador, Brazil"]},{"name":"Servi\u00e7o de Imunologia da Universidade Federal da Bahia","place":["Salvador, Brazil"]},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Doen\u00e7as Tropicais","place":["Salvador, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana dos Santos","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Imunologia da Universidade Federal da Bahia","place":["Salvador, Brazil"]},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Doen\u00e7as Tropicais","place":["Salvador, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Khouri","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade da Universidade Federal da Bahia","place":["Salvador, Brazil"]},{"name":"Laborat\u00f3rio de Medicina e Sa\u00fade P\u00fablica de Precis\u00e3o \u2013 MESP\u00b2 \u2013 Instituto Gon\u00e7alo Moniz-FIOCRUZ","place":["Bahia, Brazil"]},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Sa\u00fade Digital (INCT-DigiSa\u00fade)","place":["Salvador, Brazil"]},{"name":"Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Clinical and Epidemiological Virology","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Roberto","family":"Machado","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade da Universidade Federal da Bahia","place":["Salvador, Brazil"]},{"name":"Servi\u00e7o de Imunologia da Universidade Federal da Bahia","place":["Salvador, Brazil"]},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Doen\u00e7as Tropicais","place":["Salvador, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9a Cristina","family":"Castellucci","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-gradua\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade da Universidade Federal da Bahia","place":["Salvador, Brazil"]},{"name":"Servi\u00e7o de Imunologia da Universidade Federal da Bahia","place":["Salvador, Brazil"]},{"name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Doen\u00e7as Tropicais","place":["Salvador, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2022\/8652062","article-title":"Leprosy: a review of epidemiology, clinical diagnosis, and management","volume":"2022","author":"Chen","year":"2022","journal-title":"J Trop Med"},{"key":"B2","article-title":"Classification of leprosy according to immunity. a five-group system","volume":"34","author":"Ridley","year":"1966","journal-title":"Int J Lepr Other Mycobact Dis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0010476","article-title":"Understanding leprosy reactions and the impact on the lives of people affected: an exploration in two leprosy endemic countries","volume":"16","author":"Putri","year":"2022","journal-title":"PloS NeglTrop Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2018.10.003","article-title":"Evaluation of monocyte subsets and markers of activation in leprosy reactions","volume":"21","author":"Shibuya","year":"2019","journal-title":"Microbes Infect"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.47276\/lr.87.2.221","article-title":"The use of steroids and thalidomide in the management of erythema nodosum leprosum; 17 years at the hospital for tropical diseases, London","volume":"87","author":"Nabarro","year":"2016","journal-title":"Lepr Rev"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1590\/s0074-02762011000700012","article-title":"Schistosoma mansoni antigens alter the cytokine response in vitro during cutaneous leishmaniasis","volume":"106","author":"Bafica","year":"2011","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/nm1430","article-title":"Tetraspanins on the surface of schistosoma mansoni are protective antigens against schistosomiasis","volume":"12","author":"Tran","year":"2006","journal-title":"Nat Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/520308","article-title":"Changes in T-cell and monocyte phenotypes in vitro by schistosoma mansoni antigens in cutaneous leishmaniasis patients","volume":"2012","author":"Bafica","year":"2012","journal-title":"J Parasitol Res"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1159\/000348700","article-title":"Schistosoma antigens downmodulate the in vitro inflammatory response in individuals infected with human T cell lymphotropic virus type 1","volume":"20","author":"Lima","year":"2013","journal-title":"Neuroimmunomodulation"},{"key":"B10","doi-asserted-by":"publisher","first-page":"73","DOI":"10.2174\/187152810791292836","article-title":"Immunomodulation of the allergic inflammatory response: new developments","volume":"9","author":"Araujo","year":"2010","journal-title":"Inflammation Allergy Drug Targets"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2016.12.002","article-title":"Schistosoma mansoni antigens alter activation markers and cytokine profile in lymphocytes of patients with asthma","volume":"166","author":"De Almeida","year":"2017","journal-title":"Acta Trop"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2024.107206","article-title":"Use of topical rSm29 in combination with intravenous meglumine antimoniate in the treatment of cutaneous leishmaniasis: a randomized controlled trial","volume":"147","author":"Lago","year":"2024","journal-title":"Int J Infect Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts356","article-title":"RSeQC: quality control of RNA-seq experiments","volume":"28","author":"Wang","year":"2012","journal-title":"Bioinformatics"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: summarize analysis results for multiple tools and samples in a single report","volume":"32","author":"Ewels","year":"2016","journal-title":"Bioinformatics"},{"key":"B15","doi-asserted-by":"publisher","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":"B16","doi-asserted-by":"publisher","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":"B17","doi-asserted-by":"publisher","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":"B18","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0114-2","article-title":"Determining cell type abundance and expression from bulk tissues with digital cytometry","volume":"37","author":"Newman","year":"2019","journal-title":"Nat Biotechnol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.jdermsci.2016.01.001","article-title":"Integrative analyses of leprosy susceptibility genes indicate a common autoimmune profile","volume":"82","author":"Zhang","year":"2016","journal-title":"J Dermatol Sci"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.09.002","article-title":"Divergence of macrophage phagocytic and antimicrobial programs in leprosy","volume":"6","author":"Montoya","year":"2009","journal-title":"Cell Host Microbe"},{"key":"B22","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/j.cell.2017.07.030","article-title":"A macrophage response to mycobacterium leprae phenolic glycolipid initiates nerve damage in leprosy","volume":"170","author":"Madigan","year":"2017","journal-title":"Cell"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0560.1998.tb01736.x","article-title":"Multibacillary leprosy: lesions with macrophages positive for S100 protein and dendritic cells positive for factor 13a","volume":"25","author":"Cuevas-Santos","year":"1998","journal-title":"J Cutan Pathol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1186\/1476-511x-13-119","article-title":"Serological responses to prednisolone treatment in leprosy reactions: study of TNF-\u03b1, antibodies to phenolic glycolipid-1, lipoarabinomanan, ceramide and S100-B","volume":"13","author":"Raju","year":"2014","journal-title":"Lipids Health Dis"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/743069","article-title":"Dendritic cell profile induced by schistosoma mansoni antigen in cutaneous leishmaniasis patients","volume":"2014","author":"Lopes","year":"2014","journal-title":"BioMed Res Int"},{"key":"B26","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1590\/s0074-02762004000900005","article-title":"Schistosoma mansoni infection modulates the immune response against allergic and auto-immune diseases","volume":"99","author":"Ara\u00fajo","year":"2004","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1590\/0074-02760230129","article-title":"Different profiles of chemokines, cytokines and cell growth factors in plasma samples from patients with leprosy, leprosy reactions and households contacts","volume":"119","author":"De Carvalho","year":"2024","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2017.05.020","article-title":"Cytokines as biomarkers to monitoring the impact of multidrug therapy in immune response of leprosy patients","volume":"97","author":"Cassirer-Costa","year":"2017","journal-title":"Cytokine"},{"key":"B29","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1590\/s0100-879x1998000100009","article-title":"Expression and cytokine secretion in the states of immune reactivation in leprosy","volume":"31","author":"Sampaio","year":"1998","journal-title":"Braz J Med Biol Res"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.2147\/ott.s216829","article-title":"Demethylation and overexpression of CSF2 are involved in immune response, chemotherapy resistance, and poor prognosis in colorectal cancer oncotargets and therapy","volume":"12","author":"Xu","year":"2019","journal-title":"OncoTargets Ther"},{"key":"B31","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1186\/s12879-018-3348-6","article-title":"Whole blood profiling of leprosy type 1(reversal) reactions highlights prominence of innate immune response genes","volume":"18","author":"R\u00eago","year":"2018","journal-title":"BMC Infect Dis"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1167-3","article-title":"Inhibition of PTGS1 promotes osteogenic differentiation of adipose-derived stem cells by suppressing NF-kB signaling","volume":"10","author":"Wang","year":"2019","journal-title":"Stem Cell Res Ther"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064748","article-title":"Gene expression profiling specifies chemokine, mitochondrial and lipid metabolism signatures in leprosy","volume":"8","author":"Guerreiro","year":"2013","journal-title":"PloS One"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2024.105298","article-title":"Association of CC-chemokine ligand-2 gene polymorphisms with leprosy reactions","volume":"26","author":"Biswas","year":"2024","journal-title":"Microbes Infec"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis208","article-title":"Genetic and immunological evidence implicates interleukin 6 as a susceptibility gene for leprosy type 2 reaction","volume":"205","author":"Sousa","year":"2012","journal-title":"J Infect Dis"},{"key":"B36","first-page":"1","volume-title":"National strategy to combat leprosy 2024\u20132030 [electronic resource]","year":"2024"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1272404","article-title":"Case report: cyclophosphamide pulse therapy for chronic recalcitrant erythema nodosum leprosum","volume":"10","author":"MaChado","year":"2023","journal-title":"Front Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1844112\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T04:18:56Z","timestamp":1780287536000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1844112\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,1]]},"references-count":37,"alternative-id":["10.3389\/fimmu.2026.1844112"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1844112","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,1]]},"article-number":"1844112"}}