{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T06:15:55Z","timestamp":1778652955471,"version":"3.51.4"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Brucella (B.)<\/jats:italic>\n                      abortus is an intracellular pathogen that causes chronic infection and remains difficult to treat. In this study, desipramine (DMI) was investigated as a potential host-directed therapeutic strategy to control\n                      <jats:italic>Brucella<\/jats:italic>\n                      infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The effects of DMI on B. abortus infection were evaluated using RAW 264.7 macrophages and an in vivo ICR mouse model. Bacterial growth, uptake, and intracellular survival were assessed in macrophages. Gene expression and signaling pathway analyses were performed to investigate immunomodulatory mechanisms. Infected-mice were treated with DMI, and bacterial loads in target organs, as well as immune responses, were examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      DMI exhibited a direct inhibitory effect against\n                      <jats:italic>Brucella<\/jats:italic>\n                      growth as well as on the bacterial uptake and intracellular survival within macrophages. This effect was accompanied by increased expression of genes that are known to play crucial roles in the control of\n                      <jats:italic>Brucella<\/jats:italic>\n                      infection. Furthermore, DMI treatment resulted in the suppression of phospho-ERK1\/2, MALT1 and Bcl10 protein expression, suggesting that the disruption of Brucella phagocytosis trafficking involves downstream signaling pathways regulated by these proteins. Notably, DMI treatment in\n                      <jats:italic>Brucella<\/jats:italic>\n                      -infected mice significantly reduced bacterial loads in the spleen and showed a decreasing trend in the liver, along with enhanced Th1-associated immune responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Together, these findings indicate that DMI exhibits both bactericidal and immunomodulatory effects beneficial to the prevention, treatment, and control of\n                      <jats:italic>Brucella<\/jats:italic>\n                      infection.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2026.1779164","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T05:55:43Z","timestamp":1778651743000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Desipramine treatment disrupts phagocytic and intracellular survival of Brucella abortus 544 in RAW 264.7 cells and promotes bacterial resistance with enhanced immune responses in ICR mice"],"prefix":"10.3389","volume":"13","author":[{"given":"Tran Xuan Ngoc","family":"Huy","sequence":"first","affiliation":[{"name":"HUTECH Institute of Applied Sciences, HUTECH University","place":["Ho Chi Minh City, Vietnam"]},{"name":"Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University","place":["Jinju, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Said Abdi","family":"Salad","sequence":"additional","affiliation":[{"name":"Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University","place":["Jinju, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trang Thi","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University","place":["Jinju, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ched Nicole Turbela","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University","place":["Jinju, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eoin Quiatchon","family":"Lajara","sequence":"additional","affiliation":[{"name":"Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University","place":["Jinju, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wongi","family":"Min","sequence":"additional","affiliation":[{"name":"Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University","place":["Jinju, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hu Jang","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University","place":["Jinju, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alisha Wehdnesday Bernardo","family":"Reyes","sequence":"additional","affiliation":[{"name":"Department of Veterinary Paraclinical Sciences, College of Veterinary Medicine, University of the Philippines Los Ba\u00f1os, College","place":["Laguna, Philippines"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suk","family":"Kim","sequence":"additional","affiliation":[{"name":"Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University","place":["Jinju, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"103031","DOI":"10.1016\/j.jiph.2025.103031","article-title":"The clinical manifestations and laboratory test results of Brucella melitensis and Brucella abortus in acute brucellosis patients","author":"Li","year":"2025","journal-title":"J Infect Public Health"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1621230","DOI":"10.3389\/fcimb.2025.1621230","article-title":"Brucellosis: bacteriology, pathogenesis, epidemiology and role of the metallophores in virulence: a 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