{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:20:38Z","timestamp":1787167238540,"version":"build-2736575974"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T00:00:00Z","timestamp":1723075200000},"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                      Postpartum endometritis is a prevalent reproductive disorder in bovines, leading to a prolonged open period, infertility, and other complications. While\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      strains can mitigate these conditions by reducing uterine inflammation, their effectiveness is limited due to a lack of direct anti microbial action and extended treatment duration. This study aimed to construct a recombinant\n                      <jats:italic>Lactobacillus johnsonii<\/jats:italic>\n                      strain expressing bovine Granulocyte-macrophage colony-stimulating factor (GM-CSF) to evaluate its potential in reducing postpartum uterine inflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The recombinant\n                      <jats:italic>Lactobacillus johnsonii<\/jats:italic>\n                      strain was engineered to express bovine GM-CSF and administered to pregnant mice via vaginal perfusion. Postpartum endometritis was induced using\n                      <jats:italic>E. coli<\/jats:italic>\n                      infection, and the protective effects of the engineered strain were assessed. Inflammatory markers (IL-6, IL-1\u03b2, TNF-\u03b1), myeloperoxidase (MPO) activity, and nitric oxide (NO) concentration were measured. Histological examination was performed to evaluate uterine morphology and pathological damage.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The recombinant\n                      <jats:italic>L. johnsonii<\/jats:italic>\n                      strain expressing GM-CSF significantly reduced inflammation levels induced by\n                      <jats:italic>E. coli<\/jats:italic>\n                      infection in the uterus. This reduction was evidenced by decreased expression of IL-6, IL-1\u03b2, TNF-\u03b1, as well as reduced MPO activity and NO concentration. Histological examination revealed improved uterine morphology and reduced pathological damage in mice treated with the recombinant GM-CSF strain. Crucially, the recombinant strain also exerts beneficial effects on bovine endometritis by reducing levels of inflammatory cytokines, suggesting a beneficial effect on clinical bovine endometritis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The recombinant\n                      <jats:italic>Lactobacillus johnsonii<\/jats:italic>\n                      expressing GM-CSF demonstrated protective effects against postpartum endometritis in bovines by reducing inflammatory cytokines. The findings indicate the potential clinical application of this engineered strain in preventing postpartum uterine inflammation, offering a novel and effective protective option for related disorders and improving bovine reproductive efficiency.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2024.1418091","type":"journal-article","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T01:06:55Z","timestamp":1723079215000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Protective effects of engineered Lactobacillus johnsonii expressing bovine granulocyte-macrophage colony-stimulating factor on bovine postpartum endometritis"],"prefix":"10.3389","volume":"11","author":[{"given":"Jing","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengkun","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhile","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfa","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"995","DOI":"10.3168\/jds.S0022-0302(97)76025-9","article-title":"Ovarian follicular cysts in dairy cows","volume":"80","author":"Garverick","year":"1997","journal-title":"J Dairy Sci"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1016\/j.theriogenology.2015.09.054","article-title":"Potential of lactic acid bacteria at regulating Escherichia coli infection and inflammation of bovine endometrium","volume":"85","author":"Gen\u00eds","year":"2016","journal-title":"Theriogenology"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1093\/aje\/kws247","article-title":"Dairy-food, calcium, magnesium, and vitamin D intake and endometriosis: a prospective cohort study","volume":"177","author":"Harris","year":"2013","journal-title":"Am J Epidemiol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"177","DOI":"10.20960\/nh.04909","article-title":"The importance of nutrition in the prevention of endometriosis: systematic review","volume":"40","author":"Zaragoza-Marti","year":"2023","journal-title":"Nutr Hosp"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.theriogenology.2020.01.042","article-title":"Modulation of immune function in the bovine uterus peripartum","volume":"150","author":"Pascottini","year":"2020","journal-title":"Theriogenology."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.vetimm.2006.03.022","article-title":"Neutrophil function and energy status in Holstein cows with uterine health disorders","volume":"113","author":"Hammon","year":"2006","journal-title":"Vet Immunol Immunopathol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1210\/en.2005-1113","article-title":"Expression and function of Toll-like receptor 4 in the endometrial cells of the uterus","volume":"147","author":"Herath","year":"2006","journal-title":"Endocrinology"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"2926","DOI":"10.3168\/jds.2009-2551","article-title":"Association between uterine disease and indicators of neutrophil and systemic energy status in lactating Holstein cows","volume":"93","author":"Galv\u00e3o","year":"2010","journal-title":"J Dairy Sci"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1017\/S1751731114000524","article-title":"Reproductive tract inflammatory disease in postpartum dairy cows","volume":"8","author":"LeBlanc","year":"2014","journal-title":"Animal"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1111\/j.1439-0531.2012.02104.x","article-title":"Immunity and inflammation in the uterus","volume":"47","author":"Turner","year":"2012","journal-title":"Reprod Domest Anim"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1516","DOI":"10.1016\/j.theriogenology.2005.08.021","article-title":"Defining postpartum uterine disease in cattle","volume":"65","author":"Sheldon","year":"2006","journal-title":"Theriogenology"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"2677","DOI":"10.1093\/humrep\/deaa217","article-title":"Decidua-derived granulocyte macrophage colony-stimulating factor induces polymorphonuclear myeloid-derived suppressor cells from circulating CD15+ neutrophils","volume":"35","author":"Li","year":"2020","journal-title":"Hum Reprod"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"13360","DOI":"10.1038\/s41598-020-70302-9","article-title":"Granulocyte-macrophage colony stimulating factor (GM-CSF) is fully expressed in the genital tract, seminal plasma and spermatozoa of male pigs","volume":"10","author":"Padilla","year":"2020","journal-title":"Sci Rep"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"154850","DOI":"10.1016\/j.cyto.2019.154850","article-title":"The effects and mechanisms of GM-CSF on endometrial regeneration","volume":"125","author":"Liu","year":"2020","journal-title":"Cytokine"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.vetmic.2017.04.025","article-title":"Effects of intravaginal lactic acid bacteria on bovine endometrium: implications in uterine health","volume":"204","author":"Gen\u00eds","year":"2017","journal-title":"Vet Microbiol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"670949","DOI":"10.3389\/fvets.2021.670949","article-title":"Effect of Lactobacillus johnsonii strain SQ0048 on the TLRs-MyD88\/NF-\u03baB signaling pathway in bovine vaginal epithelial cells","volume":"8","author":"Cheng","year":"2021","journal-title":"Front Vet Sci"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1007\/s12033-011-9450-2","article-title":"Development of vaccine delivery vehicles based on lactic acid bacteria","volume":"51","author":"Tarahomjoo","year":"2012","journal-title":"Mol Biotechnol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"313","DOI":"10.3920\/BM2014.0068","article-title":"Recombinant lactic acid bacteria as delivery vectors of heterologous antigens: the future of vaccination?","volume":"6","author":"Trombert","year":"2015","journal-title":"Benef Microbes"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"479","DOI":"10.3168\/jds.2016-11671","article-title":"A combination of lactic acid bacteria regulates Escherichia coli infection and inflammation of the bovine endometrium","volume":"100","author":"Genis","year":"2017","journal-title":"J Dairy Sci"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"2786","DOI":"10.1111\/1751-7915.14127","article-title":"Baogong decoction treats endometritis in mice by regulating uterine microbiota structure and metabolites","volume":"15","author":"Ding","year":"2022","journal-title":"Microb Biotechnol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"3682","DOI":"10.3390\/molecules27123682","article-title":"The expression and bioinformatics analysis of circular RNAs in endometritis mouse uterus tissues","volume":"27","author":"Li","year":"2022","journal-title":"Molecules"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1093\/humupd\/dmad013","article-title":"Endometrial responses to bacterial and viral infection: a scoping review","volume":"29","author":"Lindsay","year":"2023","journal-title":"Hum Reprod Update"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"6649","DOI":"10.3168\/jds.2014-8462","article-title":"Invited review: antibiotic treatment of metritis in dairy cows: a systematic approach","volume":"97","author":"Haimerl","year":"2014","journal-title":"J Dairy Sci"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"34561","DOI":"10.1038\/srep34561","article-title":"Identification of TLR2\/TLR6 signalling lactic acid bacteria for supporting immune regulation","volume":"6","author":"Ren","year":"2016","journal-title":"Sci Rep"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1042\/ETLS20200348","article-title":"Antimicrobial immunotherapeutics: past, present and future","volume":"5","author":"Mercer","year":"2021","journal-title":"Emerg Top Life Sci"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/978-1-4939-0928-5_12","article-title":"Assessment of phagocytic activity of cultured macrophages using fluorescence microscopy and flow cytometry","volume":"1172","author":"Sharma","year":"2014","journal-title":"Methods Mol Biol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"901277","DOI":"10.3389\/fimmu.2022.901277","article-title":"GM-CSF: a double-edged sword in cancer immunotherapy","volume":"13","author":"Kumar","year":"2022","journal-title":"Front Immunol"},{"key":"ref28","first-page":"176","article-title":"Chronic endometritis: morphologic and clinical observations","volume":"58","author":"Greenwood","year":"1981","journal-title":"Obstet Gynecol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-3-319-57613-8_1","article-title":"The role of the immune system beyond the fight against infection","volume":"1003","author":"Sattler","year":"2017","journal-title":"Adv Exp Med Biol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1097\/ACI.0b013e328317b88b","article-title":"Lactic acid bacteria as novel adjuvant systems for prevention and treatment of atopic diseases","volume":"8","author":"Schabussova","year":"2008","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3920\/BM2019.0121","article-title":"Immune modulatory capacity of probiotic lactic acid bacteria and applications in vaccine development","volume":"11","author":"Mojgani","year":"2020","journal-title":"Benef Microbes."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"851140","DOI":"10.3389\/fcimb.2022.851140","article-title":"Bacteriocin-producing probiotic lactic acid bacteria in controlling dysbiosis of the gut microbiota","volume":"12","author":"Anjana","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1177\/1933719118804420","article-title":"Block of granulocyte-macrophage colony-stimulating factor prevents inflammation-induced preterm birth in a mouse model for parturition","volume":"26","author":"Nold","year":"2019","journal-title":"Reprod Sci"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1111\/j.1439-0442.1991.tb01060.x","article-title":"Bovine endometritis: current and future alternative therapy","volume":"38","author":"Hussain","year":"1991","journal-title":"Zentralbl Veterinarmed A"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"100781","DOI":"10.1016\/j.animal.2023.100781","article-title":"Review: postpartum reproductive disease and fertility in dairy cows","volume":"17","author":"LeBlanc","year":"2023","journal-title":"Animal"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1189\/jlb.3AB0416-189RR","article-title":"Rab27a regulates GM-CSF-dependent priming of neutrophil exocytosis","volume":"101","author":"Ramadass","year":"2017","journal-title":"J Leukoc Biol"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"5764","DOI":"10.2174\/0929867326666181213093152","article-title":"Nitric oxide in life and death of neutrophils","volume":"26","author":"Galkina","year":"2019","journal-title":"Curr Med Chem"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2024.1418091\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T01:06:57Z","timestamp":1723079217000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2024.1418091\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,8]]},"references-count":37,"alternative-id":["10.3389\/fvets.2024.1418091"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2024.1418091","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,8]]},"article-number":"1418091"}}