{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:37:20Z","timestamp":1792186640274,"version":"4.4.0"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32170110"],"award-info":[{"award-number":["32170110"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"\u5929\u6d25\u5e02\u79d1\u5b66\u6280\u672f\u5c40 | Natural Science Foundation of Tianjin Municipality","award":["22JCYBJC01060"],"award-info":[{"award-number":["22JCYBJC01060"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2023,12,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Salmonella<\/jats:italic>\n                    is one of the most important enteric pathogens worldwide, which is able to cause lethal systemic infection via survival and replication in host macrophages. Lactate, a byproduct of anaerobic or aerobic glycolysis, can induce macrophage M2 polarization, but the relationship between lactate-mediated macrophage M2 polarization and bacterial infection is poorly understood. Here, we evaluated the role of lactate and lactate-mediated macrophage M2 polarization in the pathogenicity of\n                    <jats:italic>Salmonella<\/jats:italic>\n                    . We found that lactate levels were significantly increased in\n                    <jats:italic>Salmonella<\/jats:italic>\n                    -infected macrophages, and the increased lactate was derived from the host. Macrophage and mouse infection assays showed that the addition of lactate enhanced\n                    <jats:italic>Salmonella<\/jats:italic>\n                    replication within macrophages and the colonization of mouse systemic loci, while pharmacological or genetic inhibition of host lactate production impaired\n                    <jats:italic>Salmonella<\/jats:italic>\n                    intracellular replication and its virulence in mice. Further analysis revealed that lactate promotes M2 polarization of\n                    <jats:italic>Salmonella<\/jats:italic>\n                    -infected macrophages, and the induction of macrophage M2 polarization by lactate is responsible for lactate-mediated\n                    <jats:italic>Salmonella<\/jats:italic>\n                    growth promotion. Moreover, we showed that macrophage-derived lactate induces the\n                    <jats:italic>Salmonella<\/jats:italic>\n                    pathogenicity island (SPI)-2 type III secretion system, leading to increased translocation of the SPI-2 effector SteE, which is responsible for driving M2 polarization. Overall, these findings suggest that lactate promotes\n                    <jats:italic>Salmonella<\/jats:italic>\n                    intracellular replication and systemic infection via driving macrophage M2 polarization and highlight the complex interactions between\n                    <jats:italic>Salmonella<\/jats:italic>\n                    and macrophages.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      The important enteropathogen\n                      <jats:italic>Salmonella<\/jats:italic>\n                      can cause lethal systemic infection\n                      <jats:italic>via<\/jats:italic>\n                      survival and replication in host macrophages. Lactate represents an abundant intracellular metabolite during bacterial infection, which can also induce macrophage M2 polarization. In this study, we found that macrophage-derived lactate promotes the intracellular replication and systemic infection of\n                      <jats:italic>Salmonella<\/jats:italic>\n                      . During\n                      <jats:italic>Salmonella<\/jats:italic>\n                      infection, lactate\n                      <jats:italic>via<\/jats:italic>\n                      the\n                      <jats:italic>Salmonella<\/jats:italic>\n                      type III secretion system effector SteE promotes macrophage M2 polarization, and the induction of macrophage M2 polarization by lactate is responsible for lactate-mediated\n                      <jats:italic>Salmonella<\/jats:italic>\n                      growth promotion. This study highlights the complex interactions between\n                      <jats:italic>Salmonella<\/jats:italic>\n                      and macrophages and provides an additional perspective on host-pathogen crosstalk at the metabolic interface.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02253-23","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T09:00:22Z","timestamp":1696496422000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["Lactate promotes\n                    <i>Salmonella<\/i>\n                    intracellular replication and systemic infection via driving macrophage M2 polarization"],"prefix":"10.1128","volume":"11","author":[{"given":"Xinyue","family":"Wang","sequence":"first","affiliation":[{"name":"The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, TEDA Institute of Biological Sciences and Biotechnology, Nankai University , Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6300-3140","authenticated-orcid":false,"given":"Bin","family":"Yang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, TEDA Institute of Biological Sciences and Biotechnology, Nankai University , Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangshuang","family":"Ma","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, TEDA Institute of Biological Sciences and Biotechnology, Nankai University , Tianjin, China"},{"name":"Department of Biopharmaceuticals, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University , Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Yan","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, TEDA Institute of Biological Sciences and Biotechnology, Nankai University , Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Ma","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, TEDA Institute of Biological Sciences and Biotechnology, Nankai University , Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmin","family":"Sun","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, TEDA Institute of Biological Sciences and Biotechnology, Nankai University , Tianjin, 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