{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:21:31Z","timestamp":1792113691629,"version":"4.4.0"},"reference-count":30,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5495","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2000,11,17]]},"abstract":"<jats:p>\n            Despite the fact that\n            <jats:italic>Leishmania<\/jats:italic>\n            are transmitted exclusively by sand flies, none of the experimental models of leishmaniasis have established infection via sand fly bites. Here we describe a reproducible murine model of\n            <jats:italic>Leishmania major<\/jats:italic>\n            infection transmitted by\n            <jats:italic>Phlebotomus papatasi<\/jats:italic>\n            . Prior exposure of mice to bites of uninfected sand flies conferred powerful protection against\n            <jats:italic>Leishmania major<\/jats:italic>\n            that was associated with a strong delayed-type hypersensitivity response and with interferon-\u03b3 production at the site of parasite delivery. These results have important implications for the epidemiology of cutaneous leishmaniasis and suggest a vaccination strategy against this and possibly other vector-borne diseases.\n          <\/jats:p>","DOI":"10.1126\/science.290.5495.1351","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:47:44Z","timestamp":1027763264000},"page":"1351-1354","source":"Crossref","is-referenced-by-count":284,"title":["Protection Against Cutaneous Leishmaniasis Resulting from Bites of Uninfected Sand Flies"],"prefix":"10.1126","volume":"290","author":[{"given":"Shaden","family":"Kamhawi","sequence":"first","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine","family":"Belkaid","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Govind","family":"Modi","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Rowton","sequence":"additional","affiliation":[{"name":"Department of Entomology, Walter Reed Army Institute of Research, Washington, DC 20307, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sacks","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/0014-4894(89)90177-X","volume":"69","author":"Ribeiro J. M. C.","year":"1989","unstructured":"Ribeiro J. M. C., Exp. Parasitol. 69, 104 (1989).","journal-title":"Exp. Parasitol."},{"key":"e_1_3_1_3_2","doi-asserted-by":"crossref","first-page":"311","DOI":"10.2307\/1313614","volume":"49","author":"Wikel S. K.","year":"1999","unstructured":"Wikel S. K., BioScience 49, 311 (1999).","journal-title":"BioScience"},{"key":"e_1_3_1_4_2","doi-asserted-by":"crossref","first-page":"278","DOI":"10.4269\/ajtmh.1985.34.278","volume":"34","author":"Beach R.","year":"1985","unstructured":"Beach R., Kiilu G., Leeuwenburg J., Am. J. Trop. Med. Hyg. 34, 278 (1985).","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"e_1_3_1_5_2","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/0035-9203(85)90085-9","volume":"79","author":"Pozio E.","year":"1985","unstructured":"Pozio E., Maroli M., Gradoni L., Gramiccia M., Trans. R. Soc. Trop. Med. Hyg. 79, 524 (1985).","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"e_1_3_1_6_2","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/266628a0","volume":"266","author":"Lainson R.","year":"1977","unstructured":"Lainson R., Ward R. D., Shaw J. J., Nature 266, 628 (1977).","journal-title":"Nature"},{"key":"e_1_3_1_7_2","first-page":"105","volume":"196","author":"Killick-Kendrick R.","year":"1977","unstructured":"Killick-Kendrick R., Leaney A. J., Ready P. D., Molyneux D. H., Proc. R. Soc. London 196, 105 (1977).","journal-title":"Proc. R. Soc. London"},{"key":"e_1_3_1_8_2","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1093\/jmedent\/24.4.458","volume":"24","author":"Lawyer P. G.","year":"1987","unstructured":"Lawyer P. G., Young D. G., J. Med. Entomol. 24, 458 (1987).","journal-title":"J. Med. Entomol."},{"key":"e_1_3_1_9_2","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0035-9203(90)90266-H","volume":"84","author":"Lawyer P. G.","year":"1990","unstructured":"Lawyer P. G., et al., Trans. R. Soc. Trop. Med. Hyg. 84, 229 (1990).","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"e_1_3_1_10_2","unstructured":"Female BALB\/c and C57BL\/6 mice aged 8 to 12 weeks were purchased from the Division of Cancer Treatment National Cancer Institute Frederick MD. IL-4\u2013deficient mice generated from an C57BL\/6 embryonic stem cell line were provided by N. Noben-Trauth."},{"key":"e_1_3_1_11_2","unstructured":"Two- to 4-day-old P. papatasi females were obtained from a colony initiated from field specimens collected in Saudi Arabia. Flies were infected by artificial feeding on a chick membrane at 37\u00b0C. The bloodmeal consisted of heparinized mouse blood drawn intracardially from BALB\/c mice plus penicillin (100 U\/ml) and streptomycin (100 \u03bcg\/ml) to which 2 \u00d7 10 6 to 3 \u00d7 10 6 L. major amastigotes (MHOM\/IL80\/Friedlin) clone V1 were added. The amastigotes had been harvested from BALB\/c footpads and cryopreserved in liquid nitrogen. Blood-fed flies were separated the following day and kept in an incubator at 25\u00b0 to 26\u00b0C and 85 to 95% relative humidity. They were fed on a solution of 50% sucrose 5% albumin and sterile water through soaked cotton balls. The majority of infected flies showed a heavy parasite load (mean number 60 000) a blocked stomodeal valve and a high proportion of metacyclic promastigotes (\u226530%) on days 14 to 15 after infection when they were used for transmission. Flies were placed in plastic vials (volume 3 drams; height 4.8 cm; diameter 1.8 cm) covered at one end with a 0.25-mm nylon mesh. Mice were anesthetized by intraperitoneal injection of 200 \u03bcl of ketamine hydrochloride (20 mg\/ml) (Phoenix Pharmaceuticals St. Joseph MO). Individual ears of anesthetized mice were pressed flat against the mesh surface with specially designed clamps that held the vial and ear in place between support arms adapted at the ends with a flat rubber surface. The mice were also restrained by tape across the tail and back. Five or 10 infected flies were used per ear and they were allowed to feed for 2 to 3 hours in the dark after which time each fly was examined for blood."},{"key":"e_1_3_1_12_2","unstructured":"The flies used for the pre-exposure of mice to the bites of uninfected sand flies were emergent females left without sugar or water and used the following day. For pre-exposure flies were left to feed on both ears (10 to 15 flies per ear) for a period of 30 to 40 minutes in the dark after which time at least five flies per ear became fully engorged with blood. Mice were exposed twice to uninfected flies at biweekly intervals."},{"key":"e_1_3_1_13_2","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1111\/j.1365-2915.1997.tb00406.x","volume":"11","author":"Brossard M.","year":"1997","unstructured":"Brossard M., Wikel S. K., Med. Vet. Entomol. 11, 270 (1997).","journal-title":"Med. Vet. Entomol."},{"key":"e_1_3_1_14_2","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S0020-7519(99)00042-9","volume":"29","author":"Wikel S. K.","year":"1999","unstructured":"Wikel S. K., Int. J. Parasitol. 29, 851 (1999).","journal-title":"Int. J. Parasitol."},{"key":"e_1_3_1_15_2","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/S0169-4758(99)01472-6","volume":"15","author":"Willadsen P.","year":"1999","unstructured":"Willadsen P., Jongejan F., Parasitol. Today 15, 258 (1999).","journal-title":"Parasitol. Today"},{"key":"e_1_3_1_16_2","unstructured":"Web table 1 and Web fig. 1 are available at Science Online at www.sciencemag.org\/cgi\/content\/full\/290\/5495\/1351\/DC 1."},{"key":"e_1_3_1_17_2","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1084\/jem.188.10.1941","volume":"188","author":"Belkaid Y.","year":"1998","unstructured":"Belkaid Y., et al., J. Exp. Med. 188, 1941 (1998).","journal-title":"J. Exp. Med."},{"key":"e_1_3_1_18_2","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1126\/science.3344436","volume":"239","author":"Titus R. G.","year":"1988","unstructured":"Titus R. G., Ribeiro J. M., Science 239, 1306 (1988).","journal-title":"Science"},{"key":"e_1_3_1_19_2","doi-asserted-by":"crossref","first-page":"969","DOI":"10.4049\/jimmunol.165.2.969","volume":"165","author":"Belkaid Y.","year":"2000","unstructured":"Belkaid Y., et al., J. Immunol. 165, 969 (2000).","journal-title":"J. Immunol."},{"key":"e_1_3_1_20_2","doi-asserted-by":"crossref","first-page":"5571","DOI":"10.4049\/jimmunol.161.10.5571","volume":"161","author":"Mbow M. L.","year":"1998","unstructured":"Mbow M. L., Bleyenberg J. A., Hall L. R., Titus R. G., J. Immunol. 161, 5571 (1998).","journal-title":"J. Immunol."},{"key":"e_1_3_1_21_2","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1093\/jmedent\/30.4.725","volume":"30","author":"Cross M. L.","year":"1993","unstructured":"Cross M. L., Cupp M. S., Cupp E. W., Ramberg F. B., Enriquez F. J., J. Med. Entomol. 30, 725 (1993).","journal-title":"J. Med. Entomol."},{"key":"e_1_3_1_22_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1046\/j.1365-3024.1999.00199.x","volume":"21","author":"Zeidner N. S.","year":"1999","unstructured":"Zeidner N. S., Higgs S., Happ C. M., Beaty B. J., Miller B. R., Parasite Immunol. 21, 35 (1999).","journal-title":"Parasite Immunol."},{"key":"e_1_3_1_23_2","unstructured":"Complete ears were fixed in 10% phosphate-buffered formalin and embedded in paraffin. Thin sections (5 \u03bcm) were stained with hematoxylin and eosin. The transverse section showing the greatest thickness was measured with an ocular micrometer."},{"key":"e_1_3_1_24_2","unstructured":"To obtain cells from a homogenate of the entire ear dermis the sheets were separated and placed dermal side down in Dulbecco's modified Eagle's medium (DMEM) containing penicillin (100 U\/ml) streptomycin (100 \u03bcg\/ml) and collagenase A (1 mg\/ml). After a 2-hour incubation at 37\u00b0C the dermal sheets were cut into small pieces filtered through a 70-\u03bcm nylon cell strainer and rinsed twice in RPMI containing 20% fetal bovine serum penicillin (100 U\/ml) and streptomycin (100 \u03bcg\/ml). The first rinse included 0.05% deoxyribonuclease. The leukocyte subpopulations were identified by characteristic size and granulosity combined with two-color analysis as previously described (16 29). For each sample 10 000 cells were analyzed with CELLQuest software (Becton Dickinson San Jose CA)."},{"key":"e_1_3_1_25_2","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1006\/smim.1996.0044","volume":"8","author":"Takashima A.","year":"1996","unstructured":"Takashima A., Bergstresser P. R., Semin. Immunol. 8, 333 (1996).","journal-title":"Semin. Immunol."},{"key":"e_1_3_1_26_2","unstructured":"Epidermal cells were isolated from unbitten ears and from ears 6 hours after exposure to infected P. papatasi according to a method recently described (16). Briefly the epidermis was separated from the dermis after a 30-min incubation of the dermal sheets in DMEM and 0.5 to 0.1% trypsin at 37\u00b0C. The epidermal cells were collected through a 70-\u03bcm cell strainer distributed in six-well plates and incubated in Brefeldin A (Sigma) for 6 hours at 37\u00b0C. The cells were fixed in 4% paraformaldehyde and incubated in a permeabilization buffer consisting of antibody to Fc receptor in phosphate-buffered saline containing 10% normal mouse serum and 0.1% saponin. The cells were then washed and incubated with a battery of antibodies to cytokine and their isotype controls each directly conjugated to R-phycoerythrin (Pharmingen) as specified previously (16). The stained cells were fixed again in 1% paraformaldehyde and washed and for each sample 100 000 cells were analyzed with CELLQuest software."},{"key":"e_1_3_1_27_2","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.4049\/jimmunol.156.4.1402","volume":"156","author":"Kang K.","year":"1996","unstructured":"Kang K., et al., J. Immunol. 156, 1402 (1996).","journal-title":"J. Immunol."},{"key":"e_1_3_1_28_2","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/s004030050442","volume":"291","author":"Fayyazi A.","year":"1999","unstructured":"Fayyazi A., et al., Arch. 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Sher for their critical evaluation of the manuscript."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.290.5495.1351","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T08:56:16Z","timestamp":1705136176000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.290.5495.1351"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,11,17]]},"references-count":30,"journal-issue":{"issue":"5495","published-print":{"date-parts":[[2000,11,17]]}},"alternative-id":["10.1126\/science.290.5495.1351"],"URL":"https:\/\/doi.org\/10.1126\/science.290.5495.1351","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,11,17]]}}}