{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:04:46Z","timestamp":1792008286638,"version":"4.4.0"},"reference-count":51,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T00:00:00Z","timestamp":1729814400000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Parasite Immunology"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Leishmaniasis is a neglected tropical disease, caused by protozoan parasites of <jats:italic>Leishmania<\/jats:italic> (<jats:italic>L<\/jats:italic>.), and is transmitted by bite of phlebotomine sandflies. There are several studies on central nervous system infection to indicate that <jats:italic>Leishmania<\/jats:italic> can cross the blood\u2013brain barrier, resulting in neurological manifestations, known as \u201ccerebral leishmaniasis.\u201d This study highlighted the notions: (i) polarisation of bone marrow\u2010derived macrophages (BMDM) incubated following stimulation with lipopolysaccharide (LPS) or soluble <jats:italic>Leishmania<\/jats:italic> antigen (SLA), (ii) quantification of parasites within co\u2010culture of <jats:italic>Leishmania<\/jats:italic>\u2010infected macrophages, and astrocytes, and (iii) effect of interferon\u2010gamma (IFN\u2010\u03b3) on the infection rate of co\u2010culture populations. Accordingly, 83% of overall macrophage population was identified on day 7 for CD11b and F4\/80 macrophage markers. Flow cytometry analysis revealed significant increases in CD11b and F4\/80 surface markers in LPS and SLA\u2010stimulated BMDMs at 24\u2009h, compared to untreated cells. TNF\u2010\u03b1 levels increased significantly in both LPS and SLA\u2010treated BMDMs after 48\u2009h. Additionally, SLA treatment induced a more elongated, spindle\u2010like shape in the cells, indicative of M2 macrophage polarisation over the M1 phenotype. When non\u2010infected astrocytes with\/without stimulation with IFN\u2010\u03b3 before co\u2010culture, gp63 FITC\u2010labelled parasite populations (%) in co\u2010culture decreased to 25% at 72\u2009h, thus indicating a lower infection rate in a time\u2010dependent manner. IFN\u2010\u03b3 and IL\u20106 levels significantly increased to 71.66\u2009\u00b1\u20093.51 and 184\u2009\u00b1\u200914.42\u2009pg\/mL, resulting in the inflammatory response in the co\u2010culture system at 48\u2009h (<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.0001), when compared to the control (30\u2009\u00b1\u20092.52\u2009pg\/mL for IFN\u2010\u03b3 and 8.66\u2009\u00b1\u20092.37\u2009pg\/mL for IL\u20106) at 0\u2009h of the incubation. It is the first study to emphasize the communication between <jats:italic>Leishmania<\/jats:italic>\u2010infected macrophages and astrocytes regarding <jats:italic>Leishmania<\/jats:italic> parasite load. The results suggest that astrocytes can lead to the reduction in <jats:italic>Leishmania<\/jats:italic> parasites, thereby controlling the incidence of cerebral leishmaniasis.<\/jats:p>","DOI":"10.1111\/pim.13071","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T07:44:12Z","timestamp":1729842252000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Astrocytes Can Be Key Players Against Cerebral Leishmaniasis: In\u00a0Vitro Co\u2010Culture Model for the Assessment of Infection"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4789-9095","authenticated-orcid":false,"given":"Zeynep","family":"Islek","sequence":"first","affiliation":[{"name":"Faculty of Engineering, Department of Genetics and Bioengineering Yeditepe University  Ata\u015fehir\/Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet Hikmet","family":"Ucisik","sequence":"additional","affiliation":[{"name":"Faculty of Engineering, Department of Genetics and Bioengineering Yeditepe University  Ata\u015fehir\/Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fikrettin","family":"Sahin","sequence":"additional","affiliation":[{"name":"Faculty of Engineering, Department of Genetics and Bioengineering Yeditepe University  Ata\u015fehir\/Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,25]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"World Health Organization \u201cLeishmaniasis \u201d(2024) https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/leishmaniasiss."},{"issue":"4","key":"e_1_2_12_3_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0175588","article-title":"Occurrence of Leishmania Infantum in the Central Nervous System of Naturally Infected Dogs: Parasite Load, Viability, Co\u2010Infections and Histological Alterations","volume":"12","author":"Da Costa O. V.","year":"2017","journal-title":"PLoS One"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09085-5"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2003.68.661"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.11606\/issn.1678-4456.bjvras.2007.26653"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3029"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0332-6"},{"key":"e_1_2_12_9_1","unstructured":"O. I. S.BollerandD. F.Swaab \u201cNeuroparasitology and Tropical Neurology \u201d(2013)."},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03780-z"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-011-1290-7"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1024998"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/brv.12566"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox8050121"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2023.1233762"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.1994.tb00838.x"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.10.057"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2015.02.004"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.4303\/jnp\/N110401"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.01.017"},{"key":"e_1_2_12_21_1","first-page":"1","article-title":"Novel Dual\u2010Fluorescent Flow Cytometric Approach for Quantification of Macrophages Infected With Leishmania infantum Parasites","volume":"149","author":"Islek Z.","year":"2021","journal-title":"Parasitology"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182021001530"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnano.2021.773741"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.12703\/r\/10-69"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12917-017-1174-5"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/1040638712466728"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2019.00057"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-5827.2004.tb00224.x"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0108318"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-53414-9"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01776-7"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02858"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02529"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.02682"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001763"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.5.3416"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/215283"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/pim.12586"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00614"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00264-13"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2016.06.032"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.01.027"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.10.010"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.02.013"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0327-3"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16990"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0042088"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3597"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2009.05872.x"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009027"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01881-16"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29571"}],"container-title":["Parasite Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pim.13071","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T18:51:53Z","timestamp":1730141513000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pim.13071"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10]]},"references-count":51,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1111\/pim.13071"],"URL":"https:\/\/doi.org\/10.1111\/pim.13071","archive":["Portico"],"relation":{},"ISSN":["0141-9838","1365-3024"],"issn-type":[{"value":"0141-9838","type":"print"},{"value":"1365-3024","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10]]},"assertion":[{"value":"2024-07-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13071"}}