{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T15:23:46Z","timestamp":1787844226503,"version":"build-2784847793"},"reference-count":35,"publisher":"Microbiology Society","issue":"8","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82371358"],"award-info":[{"award-number":["82371358"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Science and Technology Key Research program of Ningxia Hui Autonomous Region","award":["2023BEG02073"],"award-info":[{"award-number":["2023BEG02073"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,27]]},"abstract":"\n Introduction.<\/jats:bold>\n The persistent intracellular survival of\n Brucella<\/jats:italic>\n is a key factor contributing to immune evasion and chronic infection as evidenced by clinical recurrence. This ability of establishing long-term intracellular residency is a major driver of brucellosis relapse. Pathogens such as\n Brucella<\/jats:italic>\n often manipulate host cell polarization and exploit autophagy to sustain their intracellular survival.\n <\/jats:p>\n \n Hypothesis\/Gap Statement.<\/jats:bold>\n Real-world understanding of how macrophage polarization and autophagy jointly influence\n Brucella<\/jats:italic>\n intracellular replication remains limited, and the specific signalling pathways mediating this interaction have not been fully characterized.\n <\/jats:p>\n \n Aim.<\/jats:bold>\n This study aimed to investigate the interplay between macrophage polarization, autophagy and intracellular proliferation of\n Brucella suis<\/jats:italic>\n strain 2 and to characterize the involvement of the PI3K\/AKT\/mTOR signalling pathway in this process.\n <\/jats:p>\n \n Methodology.<\/jats:bold>\n We examined infection-induced alterations in BV2 cell polarization and autophagic activity following\n Brucella<\/jats:italic>\n S2 infection. Autophagy-related protein expression (LC3B-I, LC3B-II, ULK1 and p62) was assessed by Western blot, and autophagosome-to-autolysosome conversion was visualized by laser confocal microscopy. Macrophage polarization markers (iNOS and Arg1) and cytokine secretion (TNF-\n \u03b1<\/jats:italic>\n and IL-10) were measured by ELISA. Intracellular bacterial replication was quantified by c.f.u. assays, and pharmacological inhibitors were used to modulate PI3K\/Akt\/mTOR signalling and autophagic activity.\n <\/jats:p>\n \n Results.<\/jats:bold>\n Following\n Brucella<\/jats:italic>\n S2 infection in BV2 cells, we observed elevated expression of iNOS, Arg1, p-Akt, mTOR and autophagy-related proteins (LC3B-I, LC3B-II and ULK1), accompanied by decreased p62 levels. Laser confocal microscopy revealed efficient autophagosome-to-autolysosome conversion. Time-dependent increases in TNF-\n \u03b1<\/jats:italic>\n and IL-10 secretion indicated macrophage plasticity and the establishment of a mixed M1\/M2 phenotype. c.f.u. assays demonstrated that PI3K\/Akt\/mTOR inhibition and autophagy induction promoted\n Brucella<\/jats:italic>\n S2 intracellular proliferation. Notably, pharmacological inhibition of the PI3K\/Akt\/mTOR pathway reversed this effect by promoting M1 polarization while suppressing autophagic activity.\n <\/jats:p>\n \n Conclusion.<\/jats:bold>\n Collectively, our findings demonstrate that\n Brucella<\/jats:italic>\n S2 infection induces both M1\/M2 mixed polarization and autophagic activation in BV2 cells. Importantly, we identified that the M2-polarized state and autophagy induction synergistically promote intracellular bacterial replication, a process mediated through the PI3K\/Akt\/mTOR signalling pathway. These results suggest that targeted modulation of PI3K\/Akt\/mTOR signalling could represent a promising therapeutic approach to control\n Brucella<\/jats:italic>\n S2 intracellular proliferation.\n <\/jats:p>","DOI":"10.1099\/jmm.0.002182","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T15:15:45Z","timestamp":1787843745000},"source":"Crossref","is-referenced-by-count":0,"title":["Brucella suis vaccine strain 2 promotes intracellular proliferation by inducing M2 macrophage polarization and autophagy through PI3K\/Akt\/mTOR signalling"],"prefix":"10.1099","volume":"75","author":[{"given":"Haining","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, PR 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