{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T21:07:56Z","timestamp":1783976876933,"version":"3.55.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T00:00:00Z","timestamp":1733184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["58\/39\/20\/PHA\/BMS"],"award-info":[{"award-number":["58\/39\/20\/PHA\/BMS"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The role of autophagy in host induced by infection of parasites of the <jats:italic>Leishmania<\/jats:italic> genus remains inadequately understood. <jats:italic>Leishmania<\/jats:italic> parasites modulate host macrophages to promote its survival by inducing autophagy response in the host cell. In this study, we conducted an investigation of <jats:styled-content style=\"fixed-case\"><jats:italic>L. major<\/jats:italic><\/jats:styled-content> infection, focusing on host autophagy processes where we reconstructed two mathematical models elucidating autophagy induction and inhibition processes and its impact on parasite survival. Our models presented systems modulatory dynamics of the parasite\u2010mediated host autophagy. Our work highlighted the pivotal role of signaling molecules associated with the immune response which included signaling induced by Toll\u2010like receptor (TLR), specifically through regulation of JNK and AKT. Both molecules emerged as key regulators of host autophagy process, highlighting that JNK\/AKT signaling axis may be a potential avenue for innovative therapeutic approaches in targeting leishmaniasis. Also, ATG16L complex was identified as a critical determinant in shaping the course of leishmanial infection through formation of autophagosomes. Through in\u00a0vitro analyses in differentiated human monocyte cell line, we observed an increase in nitric oxide synthase (iNOS) concentration upon autophagy inhibition, while autophagy induction resulted in decreased iNOS concentration. This suggested that autophagy induction favors parasite survival in the host, potentially by providing a nutrient source that may be advantageous for the parasite. Inhibition of host autophagy promoted parasite elimination. Hence, our work proposed an avenue for strategically blocking host autophagy which enumerates a targeted approach for combating leishmaniasis.<\/jats:p>","DOI":"10.1111\/mmi.15333","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T19:44:42Z","timestamp":1733255082000},"page":"1-15","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Uncovering the Significance of <scp>JNK<\/scp>\/<scp>AKT<\/scp> Axis in the Autophagic Regulation of <i>Leishmania major<\/i> Infection"],"prefix":"10.1111","volume":"123","author":[{"given":"Vrushali","family":"Guhe","sequence":"first","affiliation":[{"name":"Systems Medicine Laboratory Biotechnology Research and Innovation Council\u2010National Centre for Cell Science (BRIC\u2010NCCS)  Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shailza","family":"Singh","sequence":"additional","affiliation":[{"name":"Systems Medicine Laboratory Biotechnology Research and Innovation Council\u2010National Centre for Cell Science (BRIC\u2010NCCS)  Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1752-0509-4-11"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(03)00160-9"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.1.416"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.procs.2014.05.091"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S333752"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-011-0202-5"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22179640"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2012.08.003"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200324128"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cimid.2004.03.004"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2014.291"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.28233"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl485"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1088\/0965-0393\/4\/4\/004"},{"key":"e_1_2_12_16_1","first-page":"1","article-title":"Roles of Autophagy in Elimination of Intracellular Bacterial Pathogens","volume":"4","author":"Jo E. 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