{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:56:33Z","timestamp":1785412593824,"version":"3.56.0"},"reference-count":44,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T00:00:00Z","timestamp":1778976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007061","name":"Secretar\u00eda Nacional de Ciencia, Tecnolog\u00eda e Innovaci\u00f3n (SENACYT), Panama","doi-asserted-by":"publisher","award":["NI-03-2017"],"award-info":[{"award-number":["NI-03-2017"]}],"id":[{"id":"10.13039\/501100007061","id-type":"DOI","asserted-by":"publisher"}]},{"award":["NI-03-2017"],"award-info":[{"award-number":["NI-03-2017"]}],"id":[{"id":"https:\/\/ror.org\/03gat5t60","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Sistema Nacional de Investigaci\u00f3n Panama","award":["SNI-160-2017"],"award-info":[{"award-number":["SNI-160-2017"]}]},{"name":"Sistema Nacional de Investigaci\u00f3n Panama","award":["SNI-142-2018"],"award-info":[{"award-number":["SNI-142-2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Characterizing the specific interactions of Leishmania species with different host systems is essential for the development and validation of experimental infection models and for identifying potential therapeutic targets. Leishmania parasites elicit diverse host immune responses that result in different levels of disease severity. Here, we developed a murine model of L. panamensis infection and compared the responses of BALB\/c and C57BL\/6 mice following intradermal ear inoculation. BALB\/c mice developed progressive ulcerative lesions associated with high parasite burden, whereas C57BL\/6 mice exhibited a transient edema and maintained low parasite levels detected only at early stages of infection. C57BL\/6 mice displayed early production of IL-13, IL-4, and IL-10, followed by delayed IFN-\u03b3 secretion. In contrast, BALB\/c mice showed a mixed Th1\/Th2 response at later stages of infection. Humoral responses also differed between strains, with BALB\/c mice developing an early and sustained IgG1-dominated response, while C57BL\/6 mice exhibited weak and delayed antibody production. These findings suggest that resistance to L. panamensis infection in C57BL\/6 mice is associated with an early and transient Th2\/regulatory response accompanied by a weak and delayed antibody production.<\/jats:p>","DOI":"10.3390\/pathogens15050540","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T16:07:26Z","timestamp":1779206846000},"page":"540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early Regulatory and Th2-Associated Responses Shape Resistance to Leishmania panamensis Infection in C57BL\/6 Mice"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1867-8181","authenticated-orcid":false,"given":"Lizzi","family":"Herrera","sequence":"first","affiliation":[{"name":"Centro de Biolog\u00eda Celular y Molecular de Enfermedades, Instituto de Investigaciones Cient\u00edficas y Servicios de Alta Tecnolog\u00eda (INDICASAT AIP), Ciudad del Saber, Panama City 7144, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1311-1132","authenticated-orcid":false,"given":"Carlos M.","family":"Restrepo","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Celular y Molecular de Enfermedades, Instituto de Investigaciones Cient\u00edficas y Servicios de Alta Tecnolog\u00eda (INDICASAT AIP), Ciudad del Saber, Panama City 7144, Panama"},{"name":"Sistema Nacional de Investigaci\u00f3n (SNI), Secretar\u00eda Nacional de Ciencia, Tecnolog\u00eda e Innovaci\u00f3n (SENACYT), Ciudad del Saber, Panama City 7144, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Villalobos","sequence":"additional","affiliation":[{"name":"Departamento de Patolog\u00eda, Hospital Santo Tom\u00e1s, Panama City 7127, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kissy","family":"Degracia","sequence":"additional","affiliation":[{"name":"Escuela de Biotecnolog\u00eda, Facultad de Ciencias de la Salud Dr. William C. Gorgas, Universidad Latina de Panam\u00e1, Panama City 7155, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Escuela de Biolog\u00eda, Facultad de Ciencias Naturales, Exactas y Tecnolog\u00eda, Universidad de Panam\u00e1, Panama City 7156, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0762-0566","authenticated-orcid":false,"given":"Patricia L.","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Celular y Molecular de Enfermedades, Instituto de Investigaciones Cient\u00edficas y Servicios de Alta Tecnolog\u00eda (INDICASAT AIP), Ciudad del Saber, Panama City 7144, Panama"},{"name":"Sistema Nacional de Investigaci\u00f3n (SNI), Secretar\u00eda Nacional de Ciencia, Tecnolog\u00eda e Innovaci\u00f3n (SENACYT), Ciudad del Saber, Panama City 7144, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13071-017-2028-5","article-title":"The History of Leishmaniasis","volume":"10","author":"Steverding","year":"2017","journal-title":"Parasit. Vectors"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Almeida-Souza, F., Da Silva Calabrese, K., Abreu-Silva, A.L., and Cardoso, F. (2024). Leishmania Parasites: Epidemiology, Immunopathology and Hosts, IntechOpen.","DOI":"10.5772\/intechopen.105279"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.exppara.2012.11.022","article-title":"The Histopathological and Immunological Pattern of CBA Mice Infected with Leishmania amazonensis after Treatment with Pyrazole Carbohydrazide Derivatives","volume":"133","author":"Charret","year":"2013","journal-title":"Exp. Parasitol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.jaad.2009.06.088","article-title":"New World Cutaneous Leishmaniasis: Updated Review of Current and Future Diagnosis and Treatment","volume":"63","author":"Mitropoulos","year":"2010","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/S0140-6736(18)31204-2","article-title":"Leishmaniasis","volume":"392","author":"Burza","year":"2018","journal-title":"Lancet"},{"key":"ref_6","unstructured":"(2026, March 12). Leishmaniasis. Available online: https:\/\/www.who.int\/health-topics\/leishmaniasis#tab=tab_1."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.4049\/jimmunol.1400728","article-title":"The Immunotherapeutic Role of Regulatory T Cells in Leishmania (Viannia) panamensis Infection","volume":"193","author":"Ehrlich","year":"2014","journal-title":"J. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ovalle-Bracho, C., Franco-Mu\u00f1oz, C., Londo\u00f1o-Barbosa, D., Restrepo-Montoya, D., and Clavijo-Ram\u00edrez, C. (2015). Changes in Macrophage Gene Expression Associated with Leishmania (Viannia) braziliensis Infection. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128934"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"ofy281","DOI":"10.1093\/ofid\/ofy281","article-title":"First Case of Diffuse Leishmaniasis Associated with Leishmania panamensis","volume":"5","author":"Gundacker","year":"2018","journal-title":"Open Forum Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1084\/jem.169.1.59","article-title":"Reciprocal Expression of Interferon Gamma or Interleukin 4 during the Resolution or Progression of Murine Leishmaniasis. Evidence for Expansion of Distinct Helper T Cell Subsets","volume":"169","author":"Heinzel","year":"1989","journal-title":"J. Exp. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7011","DOI":"10.1073\/pnas.88.16.7011","article-title":"Production of Interferon Gamma, Interleukin 2, Interleukin 4, and Interleukin 10 by CD4+ Lymphocytes in Vivo during Healing and Progressive Murine Leishmaniasis","volume":"88","author":"Heinzel","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/0014-4894(89)90120-3","article-title":"The Role of TH1 and TH2 Cells in Experimental Cutaneous Leishmaniasis","volume":"68","author":"Scott","year":"1989","journal-title":"Exp. Parasitol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/j.0105-2896.2004.00190.x","article-title":"Does the Leishmania Paradigm of Pathogenesis and Protection Hold for New World Cutaneous Leishmaniases or the Visceral Disease?","volume":"201","author":"Alexander","year":"2004","journal-title":"Immunol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.pt.2016.02.003","article-title":"Different Leishmania Species Drive Distinct Neutrophil Functions","volume":"32","author":"Hurrell","year":"2016","journal-title":"Trends Parasitol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1002\/eji.201546015","article-title":"The Nlrp3 Inflammasome, IL-1\u03b2, and Neutrophil Recruitment Are Required for Susceptibility to a Nonhealing Strain of Leishmania major in C57BL\/6 Mice","volume":"46","author":"Charmoy","year":"2016","journal-title":"Eur. J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2816","DOI":"10.1002\/eji.201040384","article-title":"Murine Model of Chronic L. (Viannia) panamensis Infection: Role of IL-13 in Disease","volume":"40","author":"Castilho","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5827","DOI":"10.1128\/IAI.73.9.5827-5834.2005","article-title":"Toward a Novel Experimental Model of Infection to Study American Cutaneous Leishmaniasis Caused by Leishmania braziliensis","volume":"73","author":"Novais","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Mu\u00f1oz-Durango, N., G\u00f3mez, A., Garc\u00eda-Valencia, N., Rold\u00e1n, M., Ochoa, M., Bautista-Erazo, D.E., and Ram\u00edrez-Pineda, J.R. (2022). A Mouse Model of Ulcerative Cutaneous Leishmaniasis by Leishmania (Viannia) panamensis to Investigate Infection, Pathogenesis, Immunity, and Therapeutics. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.907631"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ijpddr.2020.08.002","article-title":"Antileishmanial Activity of a New Chloroquine Analog in an Animal Model of Leishmania panamensis Infection","volume":"14","author":"Herrera","year":"2020","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Restrepo, C.M., Llanes, A., Herrera, L., Ellis, E., Lleonart, R., and Fern\u00e1ndez, P.L. (2021). Gene Expression Patterns Associated with Leishmania panamensis Infection in Macrophages from BALB\/c and C57BL\/6 Mice. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009225"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"969","DOI":"10.4049\/jimmunol.165.2.969","article-title":"A Natural Model of Leishmania Major Infection Reveals a Prolonged \u201cSilent\u201d Phase of Parasite Amplification in the Skin before the Onset of Lesion Formation and Immunity","volume":"165","author":"Belkaid","year":"2000","journal-title":"J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/0952-7915(95)80096-4","article-title":"The Protective Immune Response to Mycobacterium Tuberculosis","volume":"7","author":"Cooper","year":"1995","journal-title":"Curr. Opin. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.4049\/jimmunol.136.7.2348","article-title":"Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins","volume":"136","author":"Mosmann","year":"1986","journal-title":"J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Alexander, J., and Brombacher, F. (2012). T Helper1\/T Helper2 Cells and Resistance\/Susceptibility to Leishmania Infection: Is This Paradigm Still Relevant?. Front. Immunol., 3.","DOI":"10.3389\/fimmu.2012.00080"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.4049\/jimmunol.148.4.1182","article-title":"IL-4 Induces a Th2 Response in Leishmania major-Infected Mice","volume":"148","author":"Chatelain","year":"1992","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"100043","DOI":"10.1016\/j.cytox.2020.100043","article-title":"Unravelling the Unsolved Paradoxes of Cytokine Families in Host Resistance and Susceptibility to Leishmania Infection","volume":"2","author":"Osero","year":"2020","journal-title":"Cytokine X"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1086\/653829","article-title":"T-Bet, GATA-3, and Foxp3 Expression and Th1\/Th2 Cytokine Production in the Clinical Outcome of Human Infection with Leishmania (Viannia) Species","volume":"202","author":"Rojas","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1084\/jem.184.3.1127","article-title":"IL-4-Deficient Balb\/c Mice Resist Infection with Leishmania major","volume":"184","author":"Kopf","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.4049\/jimmunol.164.3.1458","article-title":"IL-13 Is a Susceptibility Factor for Leishmania major Infection","volume":"164","author":"Matthews","year":"2000","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6180","DOI":"10.4049\/jimmunol.161.11.6180","article-title":"Mice with STAT6-Targeted Gene Disruption Develop a Th1 Response and Control Cutaneous Leishmaniasis","volume":"161","author":"Stamm","year":"1998","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1007\/s00436-022-07539-y","article-title":"Exogenous IL-13 Exacerbates Leishmania major Infection and Abrogates Acquired Immunity to Re-Infection","volume":"121","author":"Zaatar","year":"2022","journal-title":"Parasitol. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7302","DOI":"10.4049\/jimmunol.162.12.7302","article-title":"Differences between IL-4- and IL-4 Receptor Alpha-Deficient Mice in Chronic Leishmaniasis Reveal a Protective Role for IL-13 Receptor Signaling","volume":"162","author":"Mohrs","year":"1999","journal-title":"J. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.1002\/1521-4141(200111)31:11<3255::AID-IMMU3255>3.0.CO;2-J","article-title":"IL-13 Gene-Deficient Mice Are Susceptible to Cutaneous L. mexicana Infection","volume":"31","author":"Sosa","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2923","DOI":"10.1002\/1521-4141(2002010)32:10<2923::AID-IMMU2923>3.0.CO;2-E","article-title":"An Essential Role for IL-13 in Maintaining a Non-Healing Response Following Leishmania mexicana Infection","volume":"32","author":"Alexander","year":"2002","journal-title":"Eur. J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/eji.1830210213","article-title":"Cytokine Interactions in Experimental Cutaneous Leishmaniasis. Interleukin 4 Synergizes with Interferon-Gamma to Activate Murine Macrophages for Killing of Leishmania major Amastigotes","volume":"21","author":"Bogdan","year":"1991","journal-title":"Eur. J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1093\/intimm\/9.4.467","article-title":"Effects of IL-13 on Murine Listeriosis","volume":"9","author":"Flesch","year":"1997","journal-title":"Int. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6132","DOI":"10.4049\/jimmunol.162.10.6132","article-title":"IL-4- and IL-4 Receptor-Deficient BALB\/c Mice Reveal Differences in Susceptibility to Leishmania major Parasite Substrains","volume":"162","author":"Paul","year":"1999","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.chom.2020.03.011","article-title":"Th1-Th2 Cross-Regulation Controls Early Leishmania Infection in the Skin by Modulating the Size of the Permissive Monocytic Host Cell Reservoir","volume":"27","author":"Carneiro","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Petritus, P.M., Manzoni-de-Almeida, D., Gimblet, C., Gonzalez Lombana, C., and Scott, P. (2012). Leishmania mexicana Induces Limited Recruitment and Activation of Monocytes and Monocyte-Derived Dendritic Cells Early during Infection. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001858"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6939","DOI":"10.4049\/jimmunol.1002484","article-title":"IgG1 Is Pathogenic in Leishmania mexicana Infection","volume":"185","author":"Chu","year":"2010","journal-title":"J. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1084\/jem.191.6.1063","article-title":"Internalization of Leishmania mexicana Complex Amastigotes via the Fc Receptor Is Required to Sustain Infection in Murine Cutaneous Leishmaniasis","volume":"191","author":"Kima","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1084\/jem.20041470","article-title":"A Role for IgG Immune Complexes during Infection with the Intracellular Pathogen Leishmania","volume":"201","author":"Miles","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1128\/IAI.73.4.2101-2108.2005","article-title":"Interleukin 10- and Fcgamma Receptor-Deficient Mice Resolve Leishmania mexicana Lesions","volume":"73","author":"Buxbaum","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3992","DOI":"10.4049\/jimmunol.168.8.3992","article-title":"CD8+ T Cells Are Required for Primary Immunity in C57BL\/6 Mice Following Low-Dose, Intradermal Challenge with Leishmania major","volume":"168","author":"Belkaid","year":"2002","journal-title":"J. Immunol."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/5\/540\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T16:25:47Z","timestamp":1779207947000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/5\/540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,17]]},"references-count":44,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["pathogens15050540"],"URL":"https:\/\/doi.org\/10.3390\/pathogens15050540","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,17]]}}}