{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T14:05:46Z","timestamp":1778594746148,"version":"3.51.4"},"reference-count":81,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T00:00:00Z","timestamp":1703808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Benefunder Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Previous studies have shown that the in vivo administration of soil-derived bacteria with anti-inflammatory and immunoregulatory properties, such as Mycobacterium vaccae NCTC 11659, can prevent a stress-induced shift toward an inflammatory M1 microglial immunophenotype and microglial priming in the central nervous system (CNS). It remains unclear whether M. vaccae NCTC 11659 can act directly on microglia to mediate these effects. This study was designed to determine the effects of M. vaccae NCTC 11659 on the polarization of na\u00efve BV-2 cells, a murine microglial cell line, and BV-2 cells subsequently challenged with lipopolysaccharide (LPS). Briefly, murine BV-2 cells were exposed to 100 \u00b5g\/mL whole-cell, heat-killed M. vaccae NCTC 11659 or sterile borate-buffered saline (BBS) vehicle, followed, 24 h later, by exposure to 0.250 \u00b5g\/mL LPS (Escherichia coli 0111: B4; n = 3) in cell culture media vehicle (CMV) or a CMV control condition. Twenty-four hours after the LPS or CMV challenge, cells were harvested to isolate total RNA. An analysis using the NanoString platform revealed that, by itself, M. vaccae NCTC 11659 had an \u201cadjuvant-like\u201d effect, while exposure to LPS increased the expression of mRNAs encoding proinflammatory cytokines, chemokine ligands, the C3 component of complement, and components of inflammasome signaling such as Nlrp3. Among LPS-challenged cells, M. vaccae NCTC 11659 had limited effects on differential gene expression using a threshold of 1.5-fold change. A subset of genes was assessed using real-time reverse transcription polymerase chain reaction (real-time RT-PCR), including Arg1, Ccl2, Il1b, Il6, Nlrp3, and Tnf. Based on the analysis using real-time RT-PCR, M. vaccae NCTC 11659 by itself again induced \u201cadjuvant-like\u201d effects, increasing the expression of Il1b, Il6, and Tnf while decreasing the expression of Arg1. LPS by itself increased the expression of Ccl2, Il1b, Il6, Nlrp3, and Tnf while decreasing the expression of Arg1. Among LPS-challenged cells, M. vaccae NCTC 11659 enhanced LPS-induced increases in the expression of Nlrp3 and Tnf, consistent with microglial priming. In contrast, among LPS-challenged cells, although M. vaccae NCTC 11659 did not fully prevent the effects of LPS relative to vehicle-treated control conditions, it increased Arg1 mRNA expression, suggesting that M. vaccae NCTC 11659 induces an atypical microglial phenotype. Thus, M. vaccae NCTC 11659 acutely (within 48 h) induced immune-activating and microglial-priming effects when applied directly to murine BV-2 microglial cells, in contrast to its long-term anti-inflammatory and immunoregulatory effects observed on the CNS when whole-cell, heat-killed preparations of M. vaccae NCTC 11659 were given peripherally in vivo.<\/jats:p>","DOI":"10.3390\/ijms25010474","type":"journal-article","created":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T09:15:11Z","timestamp":1703841311000},"page":"474","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of Mycobacterium vaccae NCTC 11659 and Lipopolysaccharide Challenge on Polarization of Murine BV-2 Microglial Cells"],"prefix":"10.3390","volume":"25","author":[{"given":"Luke W.","family":"Desmond","sequence":"first","affiliation":[{"name":"Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4411-5454","authenticated-orcid":false,"given":"Evan M.","family":"Holbrook","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caelan T. O.","family":"Wright","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristian A.","family":"Zambrano","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher E.","family":"Stamper","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam D.","family":"Bohr","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8613-6897","authenticated-orcid":false,"given":"Matthew G.","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA"},{"name":"Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brendan K.","family":"Podell","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie A.","family":"Moreno","sequence":"additional","affiliation":[{"name":"Prion Research Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"},{"name":"Department of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"},{"name":"Center for Healthy Aging, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew S.","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester M13 9NT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1583-7618","authenticated-orcid":false,"given":"Stefan O.","family":"Reber","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular Psychosomatics, Department of Psychosomatic Medicine and Psychotherapy, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rogelio","family":"Hern\u00e1ndez-Pando","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Patolog\u00eda Experimental, Departamento de Patolog\u00eda, Instituto Nacional De Ciencias M\u00e9dicas Y Nutrici\u00f3n Salvador Zubir\u00e1n, Ciudad de M\u00e9xico 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3920-5575","authenticated-orcid":false,"given":"Christopher A.","family":"Lowry","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA"},{"name":"Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA"},{"name":"Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA"},{"name":"Center for Microbial Exploration, University of Colorado Boulder, Boulder, CO 80309, USA"},{"name":"Department of Physical Medicine and Rehabilitation and Center for Neuroscience, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,29]]},"reference":[{"key":"ref_1","unstructured":"COVID-19 Mental Disorders Collaborators (2021). 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