{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T22:58:00Z","timestamp":1777417080593,"version":"3.51.4"},"reference-count":69,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2007,8,1]],"date-time":"2007-08-01T00:00:00Z","timestamp":1185926400000},"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":[[2007,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Cutaneous leishmaniasis is caused by protozoan parasites of the genus<jats:italic>Leishmania<\/jats:italic>. The mechanisms of pathogen control have been established primarily in the mouse model of<jats:italic>Leishmania major<\/jats:italic>infection, but they might not hold true for other<jats:italic>Leishmania<\/jats:italic>species associated with cutaneous disease. Here, we analyzed the role of cytokines, signaling components, and effector molecules in the control of New World cutaneous leishmaniasis due to<jats:italic>L. braziliensis<\/jats:italic>. Unlike<jats:italic>L. major<\/jats:italic>,<jats:italic>L. braziliensis<\/jats:italic>caused small, nonulcerative, and self-healing skin swelling in C57BL\/6 mice, as well as BALB\/c mice. In contrast to the results obtained for<jats:italic>L. mexicana<\/jats:italic>, mice deficient for interleukin-12 or its key signaling molecule, signal transducer and activator of transcription 4, rapidly succumbed to severe visceral leishmaniasis. Infection of tumor necrosis factor knockout mice with<jats:italic>L. braziliensis<\/jats:italic>led to progressive, nonhealing skin lesions with erosions and hemorrhagic ulcerations, but in contrast to the results with<jats:italic>L. major<\/jats:italic>, only 20 to 30% of the mice developed fatal visceral disease. As seen with<jats:italic>L. major<\/jats:italic>, mice with a deleted inducible nitric oxide synthase gene (iNOS<jats:sup>\u2212\/\u2212<\/jats:sup>) were unable to contain<jats:italic>L. braziliensis<\/jats:italic>in the skin, whereas the control of the parasite in the spleen remained unimpaired. Unlike what happens in<jats:italic>L. major<\/jats:italic>infections, NADPH oxidase had no impact on the course of disease in<jats:italic>L. braziliensis<\/jats:italic>-infected mice. These results not only define essential components of a protective immune response to<jats:italic>L. braziliensis<\/jats:italic>but also illustrate that the requirements for the control of cutaneous leishmaniasis vary between different parasite species.<\/jats:p>","DOI":"10.1128\/iai.01335-06","type":"journal-article","created":{"date-parts":[[2007,5,22]],"date-time":"2007-05-22T16:39:04Z","timestamp":1179851944000},"page":"3823-3832","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":67,"title":["Cytokines, Signaling Pathways, and Effector Molecules Required for the Control of<i>Leishmania<\/i>(<i>Viannia<\/i>)<i>braziliensis<\/i>in Mice"],"prefix":"10.1128","volume":"75","author":[{"given":"F. Janaina Soares","family":"Rocha","sequence":"first","affiliation":[{"name":"Institute of Clinical Microbiology, Immunology and Hygiene, University Clinic of Erlangen, Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Schleicher","sequence":"additional","affiliation":[{"name":"Institute of Clinical Microbiology, Immunology and Hygiene, University Clinic of Erlangen, Erlangen, Germany"},{"name":"Department of Medical Microbiology and Hygiene, University Clinic of Freiburg, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Mattner","sequence":"additional","affiliation":[{"name":"Institute of Clinical Microbiology, Immunology and Hygiene, University Clinic of Erlangen, Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gottfried","family":"Alber","sequence":"additional","affiliation":[{"name":"Institute of Immunology, College of Veterinary Medicine, University of Leipzig, Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Bogdan","sequence":"additional","affiliation":[{"name":"Institute of Clinical Microbiology, Immunology and Hygiene, University Clinic of Erlangen, Erlangen, Germany"},{"name":"Department of Medical Microbiology and Hygiene, University Clinic of Freiburg, Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.9.5075-5080.2002"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2003.68.527"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.5.2934"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1995.53.256"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"266","DOI":"10.4049\/jimmunol.143.1.266","volume":"143","year":"1989","unstructured":"Belosevic, M., D. S. Finbloom, P. H. van der Meide, M. V. Slayter, and C. A. Nacy. 1989. Administration of monoclonal anti-IFN-\u03b3 antibodies in vivo abrogates natural resistance of C3H\/HeN mice to infection with Leishmania major. J. Immunol.143:266-274.","journal-title":"J. Immunol."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/167.2.418"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200323825"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1001-907"},{"key":"e_1_3_2_10_2","first-page":"357","year":"2004","unstructured":"Bogdan, C. 2004. Reactive oxygen and reactive nitrogen metabolites as effector molecules against infectious pathogens, p. 357-396. In S. H. E. Kaufmann, R. Medzhitov, and S. Gordon (ed.), The innate immune response to infection. ASM Press, Washington, DC.","journal-title":"The innate immune response to infection."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0171-2985(11)80366-9"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7519(97)00169-0"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.9.5270-5277.2001"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200211)32:11<3206::AID-IMMU3206>3.0.CO;2-J"},{"key":"e_1_3_2_15_2","first-page":"233","volume":"26","year":"1993","unstructured":"Castes, M., D. Trujillo, M. E. Rojas, C. T. Fernandez, L. Araya, M. Cabrera, J. Blackwell, and J. Convit. 1993. Serum levels of tumor necrosis factor in patients with American cutaneous leishmaniasis. Biol. Res.26:233-238.","journal-title":"Biol. Res."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.9.5287-5295.2003"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1080\/00034983.1984.11811769"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01355"},{"key":"e_1_3_2_19_2","first-page":"261","volume":"17","year":"1999","unstructured":"Dedet, J.-P., F. Pratlong, G. Lanotte, and C. Ravel. 1999. The parasite. Clin. Dermatol.17:261-268.","journal-title":"Clin. Dermatol."},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.2.827-829.1998"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762004000300009"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80460-4"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.9.4561"},{"key":"e_1_3_2_24_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_25_2","doi-asserted-by":"crossref","first-page":"730","DOI":"10.4049\/jimmunol.155.2.730","volume":"155","year":"1995","unstructured":"Heinzel, F. P., R. M. Rerko, F. Ahmed, and E. Pearlman. 1995. Endogenous IL-12 is required for control of Th2 cytokine responses capable of exacerbating leishmaniasis in normally resistant mice. J. Immmunol.155:730-739.","journal-title":"J. Immmunol."},{"key":"e_1_3_2_26_2","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.4049\/jimmunol.129.5.2206","volume":"129","year":"1982","unstructured":"Howard, J. G., S. Nicklin, C. Hale, and F. Y. Liew. 1982. Prophylactic immunization against experimental leishmaniasis. I. Protection induced in mice genetically vulnerable to fatal Leishmania tropica infection. J. Immunol.129:2206-2212.","journal-title":"J. Immunol."},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1648"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2004.05.009"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.9.6085-6090.2005"},{"key":"e_1_3_2_30_2","first-page":"174","volume":"382","year":"1996","unstructured":"Kaplan, M. H., Y.-L. Sun, T. Hoey, and M. J. Grusby. 1996. Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice. Science382:174-177.","journal-title":"Science"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/icb.1996.77"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830271020"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-3416fje"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.23.10688"},{"key":"e_1_3_2_35_2","first-page":"87","volume":"2001","year":"2001","unstructured":"Lessa, H. A., P. Machado, F. Lima, A. A. Cruz, O. Bacellar, J. Guerreiro, and E. M. Carvalho. 2001. Successful treatment of refractory mucosal leishmaniasis with pentoxifylline plus antimony. Am. J. Trop. Med. Hyg.2001:87-89.","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-308X(08)60208-0"},{"key":"e_1_3_2_37_2","first-page":"71","volume":"94","year":"1999","unstructured":"Lima, G. H., G. K. DeKrey, and R. G. Titus. 1999. Resolution of an infection with Leishmania braziliensis confers complete protection to a subsequent challenge with Leishmania major in BALB\/c mice. Mem. Inst. Oswaldo Cruz94:71-76.","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-004-1193-6"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.65.11.4378-4383.1997"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830260722"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2004.00190.x"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200324391"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0776com"},{"key":"e_1_3_2_44_2","doi-asserted-by":"crossref","first-page":"3771","DOI":"10.4049\/jimmunol.163.7.3771","volume":"163","year":"1999","unstructured":"Munder, M., M. Eichmann, J. M. Moran, F. Centeno, G. Soler, and M. Modolell. 1999. Th1\/Th2-regulated expression of arginase isoforms in murine macrophages and dendritic cells. J. Immunol.163:3771-3777.","journal-title":"J. Immunol."},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.8.4916"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.4.741"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182000052379"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.4.1397"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/22.1.1"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02762007000100013"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0295-202"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.8.4638-4642.2002"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2004.02.008"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/173.3.699"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri933"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.173.1.49"},{"key":"e_1_3_2_57_2","doi-asserted-by":"crossref","first-page":"702","DOI":"10.4049\/jimmunol.137.2.702","volume":"137","year":"1986","unstructured":"Solbach, W., K. Forberg, E. Kammerer, C. Bogdan, and M. R\u00f6llinghoff. 1986. Suppressive effect of cyclosporin A on the development of Leishmania tropica-induced lesions in genetically susceptible BALB\/c mice. J. Immunol.137:702-707.","journal-title":"J. Immunol."},{"key":"e_1_3_2_58_2","first-page":"275","volume":"74","year":"2000","unstructured":"Solbach, W., and T. Laskay. 2000. The host response to Leishmania infection. Adv. Immunol.74:275-317.","journal-title":"Adv. Immunol."},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1995.53.380"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199908)29:08<2524::AID-IMMU2524>3.0.CO;2-H"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.4.1501"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.7.1231"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.2.1191-1195.2005"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3024.1985.tb00098.x"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1994.50.158"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.4.1367"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/0738-081X(96)00036-3"},{"key":"e_1_3_2_68_2","first-page":"E1628","volume":"20","year":"2006","unstructured":"Weller, K., K. Foitzik, R. Paus, W. Syska, and M. Maurer. 2006. Mast cells are required for normal healing of skin wounds in mice. FASEB J.20:E1628-E1635.","journal-title":"FASEB J."},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.6.4012"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20052288"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01335-06","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01335-06","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T23:11:45Z","timestamp":1683846705000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.01335-06"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,8]]},"references-count":69,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2007,8]]}},"alternative-id":["10.1128\/IAI.01335-06"],"URL":"https:\/\/doi.org\/10.1128\/iai.01335-06","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,8]]},"assertion":[{"value":"2006-08-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-04-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-08-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}