{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:52:10Z","timestamp":1792525930044,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0012085","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000}}],"reference-count":70,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T00:00:00Z","timestamp":1712275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca Corrente IZS SI 02\/18"],"award-info":[{"award-number":["Ricerca Corrente IZS SI 02\/18"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fanoateneo"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      In the Mediterranean basin, three\n                      <jats:italic>Leishmania<\/jats:italic>\n                      species have been identified:\n                      <jats:italic>L<\/jats:italic>\n                      .\n                      <jats:italic>infantum<\/jats:italic>\n                      ,\n                      <jats:italic>L<\/jats:italic>\n                      .\n                      <jats:italic>major<\/jats:italic>\n                      and\n                      <jats:italic>L<\/jats:italic>\n                      .\n                      <jats:italic>tropica<\/jats:italic>\n                      , causing zoonotic visceral leishmaniasis (VL), zoonotic cutaneous leishmaniasis (CL) and anthroponotic CL, respectively. Despite animal models and genomic\/transcriptomic studies provided important insights, the pathogenic determinants modulating the development of VL and CL are still poorly understood. This work aimed to identify host transcriptional signatures shared by cells infected with\n                      <jats:italic>L<\/jats:italic>\n                      .\n                      <jats:italic>infantum<\/jats:italic>\n                      ,\n                      <jats:italic>L<\/jats:italic>\n                      .\n                      <jats:italic>major<\/jats:italic>\n                      , and\n                      <jats:italic>L<\/jats:italic>\n                      .\n                      <jats:italic>tropica<\/jats:italic>\n                      , as well as specific transcriptional signatures elicited by parasites causing VL (i.e.,\n                      <jats:italic>L<\/jats:italic>\n                      .\n                      <jats:italic>infantum<\/jats:italic>\n                      ) and parasites involved in CL (i.e.,\n                      <jats:italic>L<\/jats:italic>\n                      .\n                      <jats:italic>major<\/jats:italic>\n                      ,\n                      <jats:italic>L<\/jats:italic>\n                      .\n                      <jats:italic>tropica<\/jats:italic>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methodology\/Principal findings<\/jats:title>\n                    <jats:p>\n                      U937 cells differentiated into macrophage-like cells were infected with\n                      <jats:italic>L<\/jats:italic>\n                      .\n                      <jats:italic>infantum<\/jats:italic>\n                      ,\n                      <jats:italic>L<\/jats:italic>\n                      .\n                      <jats:italic>major<\/jats:italic>\n                      and\n                      <jats:italic>L<\/jats:italic>\n                      .\n                      <jats:italic>tropica<\/jats:italic>\n                      for 24h and 48h, and total RNA was extracted. RNA sequencing, performed on an Illumina NovaSeq 6000 platform, was used to evaluate the transcriptional signatures of infected cells with respect to non-infected cells at both time points. The EdgeR package was used to identify differentially expressed genes (fold change &gt; 2 and FDR-adjusted p-values &lt; 0.05). Then, functional enrichment analysis was employed to identify the enriched ontology terms in which these genes are involved. At 24h post-infection, a common signature of 463 dysregulated genes shared among all infection conditions was recognized, while at 48h post-infection the common signature was reduced to 120 genes. Aside from a common transcriptional response, we evidenced different upregulated functional pathways characterizing\n                      <jats:italic>L<\/jats:italic>\n                      .\n                      <jats:italic>infantum<\/jats:italic>\n                      -infected cells, such as VEGFA-VEGFR2 and NFE2L2-related pathways, indicating vascular remodeling and reduction of oxidative stress as potentially important factors for visceralization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The identification of pathways elicited by parasites causing VL or CL could lead to new therapeutic strategies for leishmaniasis, combining the canonical anti-leishmania compounds with host-directed therapy.<\/jats:p>\n                  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