{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:07:24Z","timestamp":1792570044288,"version":"4.5.0"},"reference-count":78,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2003,1,1]],"date-time":"2003-01-01T00:00:00Z","timestamp":1041379200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2003,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The levels of protection found in vaccine studies of murine visceral leishmaniasis are significantly lower than for cutaneous leishmaniasis; whether this is due to the high-challenge murine model employed and\/or is a consequence of differences required in tissue-specific local immune responses is not understood. Consequently, an intradermal murine model of visceral leishmaniasis has been explored. Intradermal inoculation established a chronic infection in susceptible mice which was associated with a pattern of parasite clearance with time postinfection in the liver and skin; in contrast, parasite persistence and expansion was observed in lymphoid tissue (spleen and draining lymph node). The course of disease found appears to be similar to those reported for subclinical canine and human visceral leishmaniasis. Clearance of parasites from the skin was correlated with an inflammatory response and the infiltration and activation of CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T cells. In contrast, in lymphoid tissue (lymph node or spleen), the production of Th1\/Th2 cytokines (interleukin-4 [IL-4], IL-10, and gamma interferon) appeared to correlate with parasite burden and pathogenesis. In vaccination experiments employing the<jats:italic>Leishmania infantum<\/jats:italic>D-13 (p80) antigen, significantly higher levels of protection were found with the intradermal murine model (29 to 7,500-fold more than naive controls) than were found with a low-dose intravenous infection model (9 to 173-fold). Thus, this model should prove useful for further investigation of disease pathogenesis as well as vaccine studies of visceral leishmaniasis.<\/jats:p>","DOI":"10.1128\/iai.71.1.401-410.2003","type":"journal-article","created":{"date-parts":[[2002,12,20]],"date-time":"2002-12-20T23:07:23Z","timestamp":1040425643000},"page":"401-410","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":95,"title":["Intradermal Infection Model for Pathogenesis and Vaccine Studies of Murine Visceral Leishmaniasis"],"prefix":"10.1128","volume":"71","author":[{"given":"Saeed","family":"Ahmed","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520-8034"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Colmenares","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520-8034"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Soong","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas 77555-1019"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Goldsmith-Pestana","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520-8034"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Munstermann","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520-8034"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Molina","sequence":"additional","affiliation":[{"name":"WHO Collaborating Center for Leishmaniasis, Servicio de Parasitologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"McMahon-Pratt","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520-8034"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.6.2371-2377.1997"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200010)30:10<2935::AID-IMMU2935>3.0.CO;2-Q"},{"key":"e_1_3_2_4_2","first-page":"1427","volume":"339","year":"1992","unstructured":"Alvar, J., B. Gutierrez-Solar, R. Molina, R. Lopez-Velez, A. Garcia-Camacho, P. Martinez, F. Laguna, E. Cercenado, and A. Galmes. 1992. Prevalence of Leishmania infection among AIDS patients. Lancet339:1427.","journal-title":"Lancet"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/32588"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.10.1497"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.10.1941"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.2.969"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.3.1499-1507.2001"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0035-9203(00)90055-5"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.56.12.3272-3279.1988"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.4049\/jimmunol.151.3.1224","volume":"151","year":"1993","unstructured":"Ding, L., P. S. Linsley, L. Y. Huang, R. N. Germain, and E. M. Shevach. 1993. IL-10 inhibits macrophage costimulatory activity by selectively inhibiting the up-regulation of B7 expression. J. Immunol.151:1224-1234.","journal-title":"J. Immunol."},{"key":"e_1_3_2_13_2","unstructured":"Duboise S. M. 1994. Developmentally regulated antigens of Leishmania pifanoi amastigotes: characterization patterns of expression and immunoprophylactic potential p. 1-238. Ph.D. thesis. Yale University New Haven Conn."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199802)28:02<669::AID-IMMU669>3.0.CO;2-N"},{"key":"e_1_3_2_15_2","first-page":"64","volume":"111","year":"1998","unstructured":"Gasim, S., A. M. Elhassan, E. A. Khalil, A. Ismail, A. M. Kadaru, A. Kharazmi, and T. G. Theander. 1998. High levels of plasma IL-10 and expression of IL-10 by keratinocytes during visceral leishmaniasis predict subsequent development of post-kala-azar dermal leishmaniasis. Clin. Exp. Immunol.111:64-69.","journal-title":"Clin. Exp. Immunol."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116570"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(01)00023-8"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1086\/314520"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.4.2001"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.3.913-918.1996"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199802)28:02<687::AID-IMMU687>3.0.CO;2-N"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.4049\/jimmunol.162.3.1723","volume":"162","year":"1999","unstructured":"Groux, H., F. Cottrez, M. Rouleau, S. Mauze, S. Antonenko, S. Hurst, T. McNeil, M. Bigler, M. G. Roncarolo, and R. L. Coffman. 1999. A transgenic model to analyze the immunoregulatory role of IL-10 secreted by antigen-presenting cells. J. Immunol.162:1723-1729.","journal-title":"J. Immunol."},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.7.1137"},{"key":"e_1_3_2_24_2","doi-asserted-by":"crossref","first-page":"3501","DOI":"10.4049\/jimmunol.155.7.3501","volume":"155","year":"1995","unstructured":"Hall, L. R., and R. G. Titus. 1995. Sand fly vector saliva selectively modulates macrophage functions that inhibit killing of Leishmania major and nitric oxide production. J. Immunol.155:3501-3506.","journal-title":"J. Immunol."},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4894(87)90138-X"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.172.2.645"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.2.1141"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116372"},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.4049\/jimmunol.146.8.2763","volume":"146","year":"1991","unstructured":"Kaye, P. M., A. J. Curry, and J. M. Blackwell. 1991. Differential production of Th1- and Th2-derived cytokines does not determine the genetically controlled or vaccine-induced rate of cure in murine visceral leishmaniasis. J. Immunol.146:2763-2770.","journal-title":"J. Immunol."},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1086\/517817"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1051\/parasite\/1994014311"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.2.826-835.2002"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2613.1996.958096.x"},{"key":"e_1_3_2_34_2","doi-asserted-by":"crossref","first-page":"4537","DOI":"10.4049\/jimmunol.157.10.4537","volume":"157","year":"1996","unstructured":"Leclercq, V., M. Lebastard, Y. Belkaid, J. Louis, and G. Milon. 1996. The outcome of the parasitic process initiated by Leishmania infantum in laboratory mice: a tissue-dependent pattern controlled by the Lsh and MHC loci. J. Immunol.157:4537-4545.","journal-title":"J. Immunol."},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1089\/107999000312748"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0733-8635(18)30058-5"},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","first-page":"5571","DOI":"10.4049\/jimmunol.161.10.5571","volume":"161","year":"1998","unstructured":"Mbow, M. L., J. A. Bleyenberg, L. R. Hall, and R. G. Titus. 1998. Phlebotomus papatasi sand fly salivary gland lysate down-regulates a Th1, but up-regulates a Th2, response in mice infected with Leishmania major. J. Immunol.161:5571-5577.","journal-title":"J. Immunol."},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.1.171-178.1997"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.1996.tb00059.x"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.10.5595-5602.2000"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.8.4719-4725.2001"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.1.18-27.1998"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.3.1058-1063.1994"},{"key":"e_1_3_2_44_2","first-page":"87","volume":"51","year":"1993","unstructured":"Molina, R. 1993. Laboratory adaptation of an autochthonous colony of Phlebotmus perniciosus Newstead, 1911 (Diptera: Psychodidae). Res. Rev. Parasitol.51:87-89.","journal-title":"Res. Rev. Parasitol."},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.11.040193.001121"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.9.5226"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1997.57.216"},{"key":"e_1_3_2_48_2","doi-asserted-by":"crossref","first-page":"4153","DOI":"10.4049\/jimmunol.161.8.4153","volume":"161","year":"1998","unstructured":"Murphy, M. L., S. E. Cotterell, P. M. Gorak, C. R. Engwerda, and P. M. Kaye. 1998. Blockade of CTLA-4 enhances host resistance to the intracellular pathogen, Leishmania donovani. J. Immunol.161:4153-4160.","journal-title":"J. Immunol."},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(2001010)31:10<2848::AID-IMMU2848>3.0.CO;2-T"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.5.867"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.11.6289-6293.2000"},{"key":"e_1_3_2_52_2","doi-asserted-by":"crossref","first-page":"929","DOI":"10.4049\/jimmunol.151.2.929","volume":"151","year":"1993","unstructured":"Murray, H. W., G. D. Miralles, M. Y. Stoeckle, and D. F. McDermott. 1993. Role and effect of IL-2 in experimental visceral leishmaniasis. J. Immunol.151:929-938.","journal-title":"J. Immunol."},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1998.58.710"},{"key":"e_1_3_2_54_2","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.4049\/jimmunol.140.7.2406","volume":"140","year":"1988","unstructured":"Pan, A. A., and D. McMahon-Pratt. 1988. Monoclonal antibodies specific for the amastigote stage of Leishmania pifanoi. I. Characterization of antigens associated with stage- and species-specific determinants. J. Immunol.140:2406-2414.","journal-title":"J. Immunol."},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(01)00031-7"},{"key":"e_1_3_2_56_2","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.4049\/jimmunol.127.4.1438","volume":"127","year":"1981","unstructured":"Pearson, R. D., and R. T. Steigbigel. 1981. Phagocytosis and killing of the protozoan Leishmania donovani by human polymorphonuclear leukocytes. J. Immunol.127:1438-1443.","journal-title":"J. Immunol."},{"key":"e_1_3_2_57_2","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.4049\/jimmunol.150.6.2322","volume":"150","year":"1993","unstructured":"Rachamim, N., and C. L. Jaffe. 1993. Pure protein from Leishmania donovani protects mice against both cutaneous and visceral leishmaniasis. J. Immunol.150:2322-2331.","journal-title":"J. Immunol."},{"key":"e_1_3_2_58_2","doi-asserted-by":"crossref","first-page":"4283","DOI":"10.4049\/jimmunol.161.8.4283","volume":"161","year":"1998","unstructured":"Shibata, Y., L. A. Foster, M. Kurimoto, H. Okamura, R. M. Nakamura, K. Kawajiri, J. P. Justice, M. R. Van Scott, Q. N. Myrvik, and W. J. Metzger. 1998. Immunoregulatory roles of IL-10 in innate immunity: IL-10 inhibits macrophage production of IFN-gamma-inducing factors but enhances NK cell production of IFN-gamma. J. Immunol.161:4283-4288.","journal-title":"J. Immunol."},{"key":"e_1_3_2_59_2","doi-asserted-by":"crossref","first-page":"5374","DOI":"10.4049\/jimmunol.158.11.5374","volume":"158","year":"1997","unstructured":"Soong, L., C. H. Chang, J. Sun, B. J. Longley, Jr., N. H. Ruddle, R. A. Flavell, and D. McMahon-Pratt. 1997. Role of CD4+ T cells in pathogenesis associated with Leishmania amazonensis infection. J. Immunol.158:5374-5383.","journal-title":"J. Immunol."},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.9.3559-3566.1995"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.12.7064"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.3.1921"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.1997.tb01005.x"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.5.2628"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.7.1231"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.1993.tb00634.x"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.1985.tb00098.x"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3344436"},{"key":"e_1_3_2_69_2","doi-asserted-by":"crossref","first-page":"768","DOI":"10.4049\/jimmunol.153.2.768","volume":"153","year":"1994","unstructured":"Tumang, M. C., C. Keogh, L. L. Moldawer, D. C. Helfgott, R. Teitelbaum, J. Hariprashad, and H. W. Murray. 1994. Role and effect of TNF-alpha in experimental visceral leishmaniasis. J. Immunol.153:768-775.","journal-title":"J. Immunol."},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.1983.tb00760.x"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.57.9.2892-2899.1989"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1994.0097"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/161.6.1313"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.56.9.2385-2391.1988"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.2307\/3282344"},{"key":"e_1_3_2_76_2","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.4049\/jimmunol.156.6.2231","volume":"156","year":"1996","unstructured":"Wilson, M. E., M. Sandor, A. M. Blum, B. M. Young, A. Metwali, D. Elliott, R. G. Lynch, and J. V. Weinstock. 1996. Local suppression of IFN-gamma in hepatic granulomas correlates with tissue-specific replication of Leishmania chagasi. J. Immunol.156:2231-2239.","journal-title":"J. Immunol."},{"key":"e_1_3_2_77_2","doi-asserted-by":"crossref","first-page":"6148","DOI":"10.4049\/jimmunol.161.11.6148","volume":"161","year":"1998","unstructured":"Wilson, M. E., B. M. Young, B. L. Davidson, K. A. Mente, and S. E. McGowan. 1998. The importance of TGF-beta in murine visceral leishmaniasis. J. Immunol.161:6148-6155.","journal-title":"J. Immunol."},{"key":"e_1_3_2_78_2","unstructured":"World Health Organization. 2000. WHO report on global surveillance of epidemic-prone infectious diseases: leishmaniasis and Leishmania \/HIV co-infection vol. 2000. WHO\/CDS\/CSR\/ISR\/2000.1. [Online.] http:\/\/www.who.int\/emc-documents\/surveillance\/docs ."},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2583.2000.00190.x"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.71.1.401-410.2003","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.71.1.401-410.2003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T13:17:41Z","timestamp":1704719861000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.71.1.401-410.2003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,1]]},"references-count":78,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2003,1]]}},"alternative-id":["10.1128\/IAI.71.1.401-410.2003"],"URL":"https:\/\/doi.org\/10.1128\/iai.71.1.401-410.2003","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,1]]},"assertion":[{"value":"2002-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-10-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-01-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}