{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T12:31:23Z","timestamp":1780489883896,"version":"3.54.1"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T00:00:00Z","timestamp":1588291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Leishmania major causes cutaneous leishmaniasis. An antileishmanial vaccine for humans is unavailable. In this study, we report development of two attenuated L. major strains\u20145ASKH-HP and LV39-HP\u2014by continuous culture (high passage) of the corresponding virulent strains (low passage). Both avirulent strains showed similar changes in proteome profiles when analyzed by surface-enhanced laser desorption ionization mass spectrometry. Liquid chromatography\u2013mass spectrometry and microarray characterization of 5ASKH strains revealed substantially altered gene and protein expression profiles, respectively. Both virulent and avirulent L. major strains grew comparably in culture, but the avirulent strain survived significantly less in BALB\/c-derived peritoneal macrophages. Both attenuated strains failed to infect BALB\/c mice and elicited IFN-\u03b3, but not IL-4 and IL-10, responses. 5ASKH-HP parasites failed to induce significant infection even in severely immunocompromised- SCID or inducible NO synthase\u2013, CD40-, or IL-12\u2013deficient mice, indicating attenuation. The avirulent strain induced less IL-10, but higher IL-12, in macrophages. The avirulent strain failed to reduce CD40 relocation to the detergent-resistant membrane domain and to inhibit CD40-induced phosphorylation of the kinases Lyn and protein kinase C-\u03b2 and MAPKs MKK-3\/6 and p38MAPK or to upregulate MEK-1\/2 and ERK-1\/2 in BALB\/c-derived peritoneal macrophages. The virulent and the avirulent strains reciprocally modulated CD40-induced Ras-mediated signaling through PI-3K and Raf-1. Avirulent 5ASKH-primed BALB\/c mice were protected against virulent L. major challenge infection. The loss of virulence accompanied by substantially altered proteome profiles and the elicitation of host-protective immune responses indicate plausibly irreversible attenuation of the L. major strain and its potential use as a vaccine strain.<\/jats:p>","DOI":"10.4049\/jimmunol.1901362","type":"journal-article","created":{"date-parts":[[2020,4,3]],"date-time":"2020-04-03T18:55:43Z","timestamp":1585940143000},"page":"2734-2753","source":"Crossref","is-referenced-by-count":18,"title":["Development and Characterization of an Avirulent <i>Leishmania major<\/i> Strain"],"prefix":"10.1093","volume":"204","author":[{"given":"Mukesh Kumar","family":"Jha","sequence":"first","affiliation":[{"name":"National Centre for Cell Science, Savitribai Phule Pune University , Pune, Maharashtra 411007 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0685-4942","authenticated-orcid":false,"given":"Aditya Y","family":"Sarode","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, Savitribai Phule Pune University , Pune, Maharashtra 411007 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1040-5506","authenticated-orcid":false,"given":"Neelam","family":"Bodhale","sequence":"additional","affiliation":[{"name":"Jagadis Bose National Science Talent Search , Kolkata, West Bengal 700107 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debasri","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, Savitribai Phule Pune University , Pune, Maharashtra 411007 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3935-2655","authenticated-orcid":false,"given":"Surya Prakash","family":"Pandey","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, Savitribai Phule Pune University , Pune, Maharashtra 411007 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neetu","family":"Srivastava","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, Savitribai Phule Pune University , Pune, Maharashtra 411007 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1301-0761","authenticated-orcid":false,"given":"Abdur","family":"Rub","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, Savitribai Phule Pune University , Pune, Maharashtra 411007 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9270-2717","authenticated-orcid":false,"given":"Ricardo","family":"Silvestre","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute, School of Health Sciences, University of Minho , 4710-057 Braga ,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arup","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Trident Academy of Creative Technology , Bhubaneswar, Odisha 751024 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5833-7912","authenticated-orcid":false,"given":"Bhaskar","family":"Saha","sequence":"additional","affiliation":[{"name":"National Centre for Cell Science, Savitribai Phule Pune University , Pune, Maharashtra 411007 ,","place":["India"]},{"name":"Trident Academy of Creative Technology , Bhubaneswar, Odisha 751024 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,15]]},"reference":[{"key":"2025030417511836200_bib1","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1016\/S0140-6736(05)67629-5","article-title":"Advances in leishmaniasis","volume":"366","author":"Murray","year":"2005","journal-title":"Lancet"},{"key":"2025030417511836200_bib2","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1128\/CMR.18.2.293-305.2005","article-title":"Subversion mechanisms by which Leishmania parasites can escape the host immune response: a signaling point of view","volume":"18","author":"Olivier","year":"2005","journal-title":"Clin. 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