{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T10:17:44Z","timestamp":1789208264833,"version":"build-2803163510"},"reference-count":30,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T00:00:00Z","timestamp":1661472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"the Brazilian agencies CNPq","doi-asserted-by":"publisher","award":["435224\/2018-2"],"award-info":[{"award-number":["435224\/2018-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"the Brazilian agencies CNPq","doi-asserted-by":"publisher","award":["APQ-01373-14\u2014PRONEX"],"award-info":[{"award-number":["APQ-01373-14\u2014PRONEX"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FAPEMIG","award":["435224\/2018-2"],"award-info":[{"award-number":["435224\/2018-2"]}]},{"name":"FAPEMIG","award":["APQ-01373-14\u2014PRONEX"],"award-info":[{"award-number":["APQ-01373-14\u2014PRONEX"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The spleen plays a central role in human and canine visceral leishmaniasis, where the activation of the immune response occurs in one of the tissues where Leishmania infantum reproduces. Therefore, this organ is both a target to understand the mechanisms involved in the parasite control and a parameter for assessing the therapeutic response. In this sense, this study aimed to evaluate the main histological, immunological and parasitological aspects in the spleen of symptomatic dogs naturally infected by L. infantum treated with the therapeutic vaccine LBMPL. For this, dogs were divided into four groups: dogs uninfected and untreated (NI group); L. infantum-infected dogs that were not treated (INT group); L. infantum-infected dogs that received treatment only with monophosphoryl lipid A adjuvant (MPL group); and L. infantum-infected dogs that received treatment with the vaccine composed by L. braziliensis promastigote proteins associated with MPL adjuvant (LBMPL group). Ninety days after the therapeutics protocol, the dogs were euthanized and the spleen was collected for the proposed evaluations. Our results demonstrated a reduction of hyperplasia of red pulp and follicular area of white pulp, increased mRNA expression of IFN-\u03b3, TNF-\u03b1, IL-12 and iNOS, and decreased IL-10 and TGF-\u03b21, and intense reduction of splenic parasitism in dogs treated with the LBMPL vaccine. These results possibly suggest that the pro-inflammatory environment promoted the progressive organization of the splenic architecture favoring the cellular activation, with consequent parasite control. Along with previously obtained data, our results propose the LBMPL vaccine as a possible treatment strategy for canine visceral leishmaniasis (CVL).<\/jats:p>","DOI":"10.3390\/pathogens11090974","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T22:53:42Z","timestamp":1661813622000},"page":"974","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["LBMPL Vaccine Therapy Induces Progressive Organization of the Spleen Microarchitecture, Improved Th1 Adaptative Immune Response and Control of Parasitism in Leishmania infantum Naturally Infected Dogs"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5281-3263","authenticated-orcid":false,"given":"Bruno Mendes","family":"Roatt","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Imunopatologia, N\u00facleo de Pesquisas em Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Ouro Preto, Ouro Preto 35400-000, Minas Gerais, Brazil"},{"name":"Departamento de Ci\u00eancias Biol\u00f3gicas, Instituto de Ci\u00eancias Exatas e Biol\u00f3gicas, Universidade Federal de Ouro Preto, Ouro Preto 35400-000, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamille Mirelle","family":"de Oliveira Cardoso","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunopatologia, N\u00facleo de Pesquisas em Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Ouro Preto, Ouro Preto 35400-000, Minas Gerais, Brazil"},{"name":"Grupo de Imunologia para de Medicina, Nutri\u00e7\u00e3o, Centro Universit\u00e1rio Presidente Tancredo de Almeida Neves\u2014UNIPTAN, S\u00e3o Jo\u00e3o del Rei 36301-182, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9924-8908","authenticated-orcid":false,"given":"Levi Eduardo Soares","family":"Reis","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunopatologia, N\u00facleo de Pesquisas em Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Ouro Preto, Ouro Preto 35400-000, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel Jos\u00e9 Lucas","family":"Moreira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunopatologia, N\u00facleo de Pesquisas em Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Ouro Preto, Ouro Preto 35400-000, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Let\u00edcia Captein","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunopatologia, N\u00facleo de Pesquisas em Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Ouro Preto, Ouro Preto 35400-000, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1via","family":"de Souza Marques","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Morfopatologia, N\u00facleo de Pesquisas em Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Ouro Preto, Ouro Preto 35400-000, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7260-5899","authenticated-orcid":false,"given":"N\u00e1dia","family":"das Dores Moreira","sequence":"additional","affiliation":[{"name":"Faculdade de Ci\u00eancias M\u00e9dicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 21941-902, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7033-7686","authenticated-orcid":false,"given":"Paula Melo","family":"de Abreu Vieira","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias Biol\u00f3gicas, Instituto de 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Wkly. Epidemiol. Rec., 95, 265\u2013280."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.pt.2011.04.001","article-title":"Urban Parasitology: Visceral Leishmaniasis in Brazil","volume":"27","author":"Harhay","year":"2011","journal-title":"Trends Parasitol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Coura-Vital, W., Ker, H.G., Roatt, B.M., Aguiar-Soares, R.D.O., Leal, G.G.D.A., Moreira, N.D.D., Oliveira, L.A.M., Machado, E.M.D.M., Morais, M.H.F., and Corr\u00eaa-Oliveira, R. (2014). Evaluation of Change in Canine Diagnosis Protocol Adopted by the Visceral Leishmaniasis Control Program in Brazil and a New Proposal for Diagnosis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091009"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.rvsc.2005.09.011","article-title":"Parasite Density and Impaired Biochemical\/Hematological Status Are Associated with Severe Clinical Aspects of Canine Visceral Leishmaniasis","volume":"81","author":"Reis","year":"2006","journal-title":"Res. Vet. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"750","DOI":"10.12688\/f1000research.11120.1","article-title":"Leishmaniasis: A Review","volume":"6","author":"Arenas","year":"2017","journal-title":"F1000 Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Cavalcanti, A.S., Ribeiro-Alves, M., Pereira, L.d.O.R., Mestre, G.L., Ferreira, A.B.R., Morgado, F.N., Boit\u00e9, M.C., Cupolillo, E., Moraes, M.O., and Porrozzi, R. (2015). Parasite Load Induces Progressive Spleen Architecture Breakage and Impairs Cytokine MRNA Expression in Leishmania Infantum-Naturally Infected Dogs. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0123009"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e572","DOI":"10.1016\/j.ijid.2012.12.024","article-title":"Visceral Leishmaniasis: Host-Parasite Interactions and Clinical Presentation in the Immunocompetent and in the Immunocompromised Host","volume":"17","author":"Saporito","year":"2013","journal-title":"Int. J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"653","DOI":"10.3389\/fimmu.2020.00653","article-title":"Phenotypical Characterization of Spleen Remodeling in Murine Experimental Visceral Leishmaniasis","volume":"11","author":"Hermida","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1590\/S0037-86822010000400010","article-title":"Is Severe Visceral Leishmaniasis a Systemic Inflammatory Response Syndrome?\u2014A Case Control Study","volume":"43","author":"Costa","year":"2010","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Poulaki, A., Piperaki, E.T., and Voulgarelis, M. (2021). Effects of Visceralising Leishmania on the Spleen, Liver, and Bone Marrow: A Pathophysiological Perspective. Microorganisms, 9.","DOI":"10.3390\/microorganisms9040759"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/nri1669","article-title":"Structure and Function of the Spleen","volume":"5","author":"Mebius","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1111\/j.1365-3024.2008.01051.x","article-title":"Inflammation and Structural Changes of Splenic Lymphoid Tissue in Visceral Leishmaniasis: A Study on Naturally Infected Dogs","volume":"30","author":"Santana","year":"2008","journal-title":"Parasite Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Silva, J.S., Andrade, A.C., Santana, C.C., Santos, L.Q., de Oliveira, C.I., Veras, P.S.T., Vassallo, J., and dos-Santos, W.L.C. (2012). Low CXCL13 Expression, Splenic Lymphoid Tissue Atrophy and Germinal Center Disruption in Severe Canine Visceral Leishmaniasis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0029103"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3389\/fcimb.2018.00394","article-title":"Histological Disorganization of Spleen Compartments and Severe Visceral Leishmaniasis","volume":"8","author":"Hermida","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1590\/S0037-86822012000100027","article-title":"A Esplenectomia Na Leishmaniose Visceral Refrat\u00e1ria Ao Tratamento Cl\u00ednico: Relato de Caso","volume":"45","author":"Dutra","year":"2012","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"427","DOI":"10.3389\/fcimb.2019.00427","article-title":"An Overview of Immunotherapeutic Approaches Against Canine Visceral Leishmaniasis: What Has Been Tested on Dogs and a New Perspective on Improving Treatment Efficacy","volume":"9","author":"Leite","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3389\/fimmu.2017.00217","article-title":"A Vaccine Therapy for Canine Visceral Leishmaniasis Promoted Significant Improvement of Clinical and Immune Status with Reduction in Parasite Burden","volume":"8","author":"Roatt","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Menezes-Souza, D., Guerra-S\u00e1, R., Carneiro, C.M., Vitoriano-Souza, J., Giunchetti, R.C., Teixeira-Carvalho, A., Silveira-Lemos, D., Oliveira, G.C., Corr\u00eaa-Oliveira, R., and Reis, A.B. (2012). Higher Expression of CCL2, CCL4, CCL5, CCL21, and CXCL8 Chemokines in the Skin Associated with Parasite Density in Canine Visceral Leishmaniasis. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001566"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1590\/S0036-46651996000200001","article-title":"Histopathology and Immunocytochemical Study of Type 3 and Type 4 Complement Receptors in the Liver and Spleen of Dogs Naturally and Experimentally Infected with Leishmania (Leishmania) Chagasi","volume":"38","author":"Tafuri","year":"1996","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.vetimm.2008.10.307","article-title":"Systemic and Compartmentalized Immune Response in Canine Visceral Leishmaniasis","volume":"128","author":"Reis","year":"2009","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.cimid.2017.11.003","article-title":"Parasitic Load and Histological Aspects in Different Regions of the Spleen of Dogs with Visceral Leishmaniasis","volume":"56","author":"Bagues","year":"2018","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"De Silva, A.V.A., Figueiredo, F.B., Menezes, R.C., Mendes-Junior, A.A., De Miranda, L.H.M., Cupolillo, E., Porrozzi, R., and Morgado, F.N. (2018). Morphophysiological Changes in the Splenic Extracellular Matrix of Leishmania Infantum\u2014Naturally Infected Dogs Is Associated with Alterations in Lymphoid Niches and the CD4 + T Cell Frequency in Spleens. PLoS Negl. Trop. Dis., 2.","DOI":"10.1371\/journal.pntd.0006445"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/1756-3305-4-86","article-title":"LeishVet Guidelines for the Practical Management of Canine Leishmaniosis","volume":"4","author":"Koutinas","year":"2011","journal-title":"Parasites Vectors"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/AAC.04298-14","article-title":"Systematic Review of Biomarkers to Monitor Therapeutic Response in Leishmaniasis","volume":"59","author":"Kip","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ghimire, P.G., Ghimire, P., Adhikari, J., and Chapagain, A. (2019). A Case Report of Visceral Leishmaniasis and Malaria Co-Infection with Pancytopenia and Splenomegaly\u2014A Diagnostic Challenge. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-4478-1"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Salim, T., Sershen, C.L., and May, E.E. (2016). Investigating the Role of TNF-\u03b1 and IFN-\u03b3 Activation on the Dynamics of INOS Gene Expression in Lps Stimulated Macrophages. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153289"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1007\/s00436-010-2183-5","article-title":"Qualitative and Quantitative Immunohistochemical Evaluation of INOS Expression in the Spleen of Dogs Naturally Infected with Leishmania Chagasi","volume":"108","author":"Vieira","year":"2011","journal-title":"Parasitol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1128\/CVI.00456-09","article-title":"Immunologic Indicators of Clinical Progression during Canine Leishmania Infantum Infection","volume":"17","author":"Boggiatto","year":"2010","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.vetimm.2006.10.001","article-title":"Analysis of the Cytokine Profile in Spleen Cells from Dogs Naturally Infected by Leishmania Chagasi","volume":"115","author":"Lage","year":"2007","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7674","DOI":"10.1016\/j.vaccine.2007.08.009","article-title":"Immunogenicity of a killed Leishmania vaccine with saponin adjuvant in dogs","volume":"25","author":"Giunchetti","year":"2007","journal-title":"Vaccine"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/9\/974\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:16:03Z","timestamp":1760141763000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/9\/974"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,26]]},"references-count":30,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["pathogens11090974"],"URL":"https:\/\/doi.org\/10.3390\/pathogens11090974","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,26]]}}}