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However, the mechanism underlying the immunosuppression of piglets remains unclear. Activation of the PD-1\/PD-L1 axis has been shown to trigger host immunosuppression. Baicalin possesses anti-inflammatory and immunomodulatory functions. However, whether baicalin inhibits PD-1\/PD-L1 activation and thus alleviates host immunosuppression has not been investigated. In this study, the effect of baicalin on the attenuation of piglet immunosuppression induced by <jats:italic>G. parasuis<\/jats:italic> was evaluated. Seventy piglets were randomly divided into the control group, infection group, levamisole group, BMS-1 group, 25\u00a0mg\/kg baicalin group, 50\u00a0mg\/kg baicalin group and 100\u00a0mg\/kg baicalin group. Following pretreatment with levamisole, BMS-1 or baicalin, the piglets were challenged with 1\u2009\u00d7\u200910<jats:sup>8<\/jats:sup>\u00a0CFU of <jats:italic>G. parasuis<\/jats:italic>. Our results showed that baicalin, levamisole and BMS-1 modified routine blood indicators and biochemical parameters; downregulated IL-1\u03b2, IL-10, IL-18, TNF-\u03b1 and IFN-\u03b3 mRNA expression; and upregulated IL-2 and IL-8 mRNA expression in blood. Baicalin, levamisole and BMS-1 increased the proportions of CD3<jats:sup>+<\/jats:sup> T cells, CD3<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> T cells, CD3<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup> T cells and CD3<jats:sup>\u2013<\/jats:sup>CD21<jats:sup>+<\/jats:sup> B cells in the splenocyte population, increased the proportions of CD3<jats:sup>+<\/jats:sup> T cells, CD3<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> T cells and CD3<jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup> T cells in the blood, and inhibited PD-1\/PD-L1 and TIM-3 activation. Baicalin, levamisole and BMS-1 reduced p-PI3K, p-Akt, and p-mTOR expression, the p-MEK1\/2\/MEK1\/2 and p-ERK1\/2\/ERK1\/2 ratios and increased RAS expression. Baicalin, levamisole and BMS-1 provided substantial protection against <jats:italic>G. parasuis<\/jats:italic> challenge and relieved tissue histopathological damage. Our findings might provide new strategies for controlling <jats:italic>G. parasuis<\/jats:italic> infection and other immunosuppressive diseases.<\/jats:p>","DOI":"10.1186\/s13567-024-01355-1","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T09:05:07Z","timestamp":1722243907000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Baicalin attenuates PD-1\/PD-L1 axis-induced immunosuppression in piglets challenged with Glaesserella parasuis by inhibiting the PI3K\/Akt\/mTOR and RAS\/MEK\/ERK signalling pathways"],"prefix":"10.1186","volume":"55","author":[{"given":"Shulin","family":"Fu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiarui","family":"You","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaoli","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunjian","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronghui","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yamin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyue","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yitian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wutao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0968-232X","authenticated-orcid":false,"given":"Ling","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinsheng","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,7,29]]},"reference":[{"key":"1355_CR1","doi-asserted-by":"publisher","first-page":"751","DOI":"10.3390\/cells12050751","volume":"12","author":"F Liu","year":"2023","unstructured":"Liu F, Gao Y, Jiao J, Zhang Y, Li J, Ding L, Zhang L, Chen Z, Song X, Yang G, Yu J, Wu J (2023) Upregulation of TLR4-dependent ATP production is critical for Glaesserella parasuis LPS-mediated inflammation. 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