{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T06:09:03Z","timestamp":1784182143915,"version":"3.55.0"},"reference-count":91,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Backgrounds and aims<\/jats:title>\n                    <jats:p>Stroke-associated pneumonia (SAP) is a major infectious complication that increases mortality after stroke. Stroke-induced immunosuppression has been proposed as a key driver of SAP, supporting the rationale for immunomodulation. This review systematically outlines the immunopathology of SAP and evaluates immune-targeted strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Following PRISMA guidelines, we systematically searched PubMed, Scopus, Web of Science, and Embase for studies on the immune mechanisms and immunomodulatory therapies for SAP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We included 38 studies. Evidence from preclinical models indicates that stroke severity disrupts immune homeostasis, driving SAP through a multi-layered network. Systemic immunosuppression is primarily mediated by sympathetic nervous system (SNS) overactivation, inducing splenic atrophy, lymphocyte apoptosis, and impaired innate immune cells (e.g., iNKT cells), whereas the hypothalamic-pituitary-adrenal (HPA) axis appears to contribute less critically. Furthermore, sustained activation of the cholinergic anti-inflammatory pathway (CAP) may impair pulmonary antimicrobial defense. Active intercellular suppression, as exemplified by monocyte-mediated T cell death, has been identified as a potential mechanism that further compromises immunity. Emerging evidence also implicates disruption of the gut\u2013lung axis (e.g., intestinal barrier dysfunction and microbial dysbiosis), local pulmonary alterations, and dysregulation of key immune molecules (e.g., \u03b1-MSH, CD147) as potential contributors to SAP development. Interventions targeting these mechanisms (e.g., iNKT cell activator) have shown promise in preclinical models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This review systematically synthesizes the mechanistic basis of SAP and identifies emerging immunomodulatory interventions. While preclinical evidence is encouraging, most strategies remain experimental, and their clinical translation requires considerable further validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1856660","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:36:32Z","timestamp":1784180192000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunomodulation for stroke-associated pneumonia: a systematic review of mechanistic insight and emerging therapeutic strategies in animal models"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiangyun","family":"Chen","sequence":"first","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]},{"name":"Institute for Brain Disorders, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihe","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghong","family":"Gao","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]},{"name":"Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxing","family":"Lai","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]},{"name":"Institute for Brain Disorders, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rufan","family":"Xu","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]},{"name":"Institute for Brain Disorders, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongrui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]},{"name":"Institute for Brain Disorders, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]},{"name":"Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]},{"name":"Institute for Brain Disorders, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Gao","sequence":"additional","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]},{"name":"Institute for Brain Disorders, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1649503","article-title":"Global burden of stroke","volume":"38","author":"Katan","year":"2018","journal-title":"Semin Neurol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70031-5","article-title":"Preventing stroke: saving lives around the world","volume":"6","author":"Strong","year":"2007","journal-title":"Lancet Neurol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s11910-016-0679-9","article-title":"Impact of infection on stroke morbidity and outcomes","volume":"16","author":"Miller","year":"2016","journal-title":"Curr Neurol Neurosci Rep"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-11-110","article-title":"Post-stroke infection: a systematic review and meta-analysis","volume":"11","author":"Westendorp","year":"2011","journal-title":"BMC Neurol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1186\/s12964-024-01905-2","article-title":"RNF13 protects neurons against ischemia-reperfusion injury via stabilizing p62-mediated Nrf2\/HO-1 signaling pathway","volume":"22","author":"Wang","year":"2024","journal-title":"Cell Commun Signal"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26178336","article-title":"Immunological mechanisms and therapeutic strategies in cerebral ischemia-reperfusion injury: from inflammatory response to neurorepair","volume":"26","author":"Li","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202509906","article-title":"TRIM56 aggravates cerebral ischemia-reperfusion injury via inhibiting KLF4-activated ferroptosis signaling","volume":"13","author":"Wang","year":"2025","journal-title":"Adv Sci (Weinh)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0060280","article-title":"The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing","volume":"6","author":"Dethlefsen","year":"2008","journal-title":"PloS Biol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.011800","article-title":"Depletion of cultivatable gut microbiota by broad-spectrum antibiotic pretreatment worsens outcome after murine stroke","volume":"47","author":"Winek","year":"2016","journal-title":"Stroke"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/s0966-842x(00)01873-4","article-title":"What is antibiotic resistance and how can we measure it","volume":"8","author":"Davison","year":"2000","journal-title":"Trends Microbiol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD008530.pub3","article-title":"Antibiotic therapy for preventing infections in people with acute stroke","volume":"1","author":"Vermeij","year":"2018","journal-title":"Cochrane Database Syst Rev"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000258346.68966.9d","article-title":"Infection after acute ischemic stroke: a manifestation of brain-induced immunodepression","volume":"38","author":"Chamorro","year":"2007","journal-title":"Stroke"},{"key":"B13","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.neuint.2018.01.002","article-title":"Research progress in stroke-induced immunodepression syndrome (SIDS) and stroke-associated pneumonia (SAP)","volume":"114","author":"Liu","year":"2018","journal-title":"Neurochem Int"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-14-43","article-title":"SYRCLE's risk of bias tool for animal studies","volume":"14","author":"Hooijmans","year":"2014","journal-title":"BMC Med Res Methodol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbih.2021.100393","article-title":"The role of \u03b22 adrenergic receptor on infection development after ischaemic stroke","volume":"18","author":"Shim","year":"2021","journal-title":"Brain Behav Immun Health"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1126\/science.1210301","article-title":"Functional innervation of hepatic iNKT cells is immunosuppressive following stroke","volume":"334","author":"Wong","year":"2011","journal-title":"Science"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021098","article-title":"Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation","volume":"198","author":"Prass","year":"2003","journal-title":"J Exp Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1007\/s12975-019-00738-3","article-title":"Stroke severity, and not cerebral infarct location, increases the risk of infection","volume":"11","author":"Shim","year":"2019","journal-title":"Trans Stroke Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.767155","article-title":"Dynamic process of secondary pulmonary infection in mice with intracerebral hemorrhage","volume":"12","author":"Zhang","year":"2021","journal-title":"Front Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-014-9839-8","article-title":"Modulation of LPS-stimulated pulmonary inflammation by Borneol in murine acute lung injury model","volume":"37","author":"Zhong","year":"2014","journal-title":"Inflammation"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.155190","article-title":"Fuzhengjiedu formula exerts protective effect against LPS-induced acute lung injury via gut-lung axis","volume":"123","author":"Lu","year":"2024","journal-title":"Phytomedicine: Int J Phytotherapy Phytopharmacology"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.549618","article-title":"The spectrum of systemic immune alterations after murine focal ischemia: immunodepression versus immunomodulation","volume":"40","author":"Liesz","year":"2009","journal-title":"Stroke"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.2014.877841","article-title":"The role of neuroendocrine pathways in prognosis after stroke","volume":"14","author":"El Husseini","year":"2014","journal-title":"Expert Rev Neurother"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000240409.68739.2b","article-title":"Stroke propagates bacterial aspiration to pneumonia in a model of cerebral ischemia","volume":"37","author":"Prass","year":"2006","journal-title":"Stroke"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15051","article-title":"Adrenergic-mediated loss of splenic marginal zone B cells contributes to infection susceptibility after stroke","volume":"8","author":"McCulloch","year":"2017","journal-title":"Nat Commun"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.02.015","article-title":"Brain ischemia suppresses immunity in the periphery and brain via different neurogenic innervations","volume":"46","author":"Liu","year":"2017","journal-title":"Immunity"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2014.05.015","article-title":"Differential effects of sympathetic nervous system and hypothalamic-pituitary-adrenal axis on systemic immune cells after severe experimental stroke","volume":"41","author":"Mracsko","year":"2014","journal-title":"Brain Behavior Immun"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600217","article-title":"Experimental stroke induces massive, rapid activation of the peripheral immune system","volume":"26","author":"Offner","year":"2006","journal-title":"J Cereb Blood Flow Metabolism: Off J Int Soc Cereb Blood Flow Metab"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.012231","article-title":"Preadmission use of glucocorticoids and 30-day mortality after stroke","volume":"47","author":"Sundb\u00f8ll","year":"2016","journal-title":"Stroke"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/bf03402177","article-title":"The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation","volume":"9","author":"Pavlov","year":"2003","journal-title":"Mol Med (Cambridge Mass)"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-197384","article-title":"Stroke-induced activation of the \u03b17 nicotinic receptor increases Pseudomonas aeruginosa lung injury","volume":"26","author":"Lafargue","year":"2012","journal-title":"FASEB J"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.008989","article-title":"Cholinergic pathway suppresses pulmonary innate immunity facilitating pneumonia after stroke","volume":"46","author":"Engel","year":"2015","journal-title":"Stroke"},{"key":"B33","doi-asserted-by":"publisher","first-page":"253","DOI":"10.3390\/vaccines8020253","article-title":"Impact of key nicotinic achr subunits on post-stroke pneumococcal pneumonia","volume":"8","author":"Jagdmann","year":"2020","journal-title":"Vaccines"},{"key":"B34","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1016\/j.immuni.2021.02.004","article-title":"Post-injury immunosuppression and secondary infections are caused by an AIM2 inflammasome-driven signaling cascade","volume":"54","author":"Roth","year":"2021","journal-title":"Immunity"},{"key":"B35","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1186\/s13054-018-2164-0","article-title":"Focal ischemic stroke leads to lung injury and reduces alveolar macrophage phagocytic capability in rats","volume":"22","author":"Samary","year":"2018","journal-title":"Crit Care"},{"key":"B36","doi-asserted-by":"publisher","first-page":"3622","DOI":"10.1038\/s41598-019-40392-1","article-title":"Ischaemic stroke in mice induces lung inflammation but not acute lung injury","volume":"9","author":"Austin","year":"2019","journal-title":"Sci Rep"},{"key":"B37","doi-asserted-by":"publisher","first-page":"6260102","DOI":"10.1155\/2022\/6260102","article-title":"NLRP3 knockout protects against lung injury induced by cerebral ischemia-reperfusion","volume":"2022","author":"Xu","year":"2022","journal-title":"Oxid Med Cell Longevity"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2024.1511638","article-title":"Pulmonary consequences of experimentally induced stroke: differences between global and focal cerebral ischemia","volume":"15","author":"Somogyi","year":"2024","journal-title":"Front Physiol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"4562","DOI":"10.1093\/brain\/awaf254","article-title":"Brain regulation of pulmonary dysfunction induced by stroke","volume":"148","author":"Chen","year":"2025","journal-title":"Brain"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.277","article-title":"Ischemic stroke alters immune cell niche and chemokine profile in mice independent of spontaneous bacterial infection","volume":"7","author":"Farris","year":"2019","journal-title":"Immun Inflammation Dis"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2100997","article-title":"Lung imaging reveals stroke-induced impairment in pulmonary intravascular neutrophil function, a response exacerbated with aging","volume":"208","author":"Wen","year":"2022","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4194","article-title":"Translocation and dissemination of commensal bacteria in post-stroke infection","volume":"22","author":"Stanley","year":"2016","journal-title":"Nat Med"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.123.042755","article-title":"Poststroke lung infection by opportunistic commensal bacteria is not mediated by their expansion in the gut microbiota","volume":"54","author":"Diaz-Marugan","year":"2023","journal-title":"Stroke"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2008.01.006","article-title":"Alpha-MSH promotes spontaneous post-ischemic pneumonia in mice via melanocortin-receptor-1","volume":"210","author":"Schulte-Herbr\u00fcggen","year":"2008","journal-title":"Exp Neurol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s12974-019-1426-3","article-title":"CD200-CD200R1 inhibitory signaling prevents spontaneous bacterial infection and promotes resolution of neuroinflammation and recovery after stroke","volume":"16","author":"Ritzel","year":"2019","journal-title":"J Neuroinflamm"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00853","article-title":"Inhibition of CD147 attenuates stroke-associated pneumonia through modulating lung immune response in mice","volume":"10","author":"Jin","year":"2019","journal-title":"Front Neurol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12980","article-title":"Advanced age promotes colonic dysfunction and gut-derived lung infection after stroke","volume":"18","author":"Wen","year":"2019","journal-title":"Aging Cell"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1203646","article-title":"As an inhibitor of norepinephrine release, dexmedetomidine provides no improvement on stroke-associated pneumonia in mice","volume":"14","author":"Zhou","year":"2023","journal-title":"Front Pharmacol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"295","DOI":"10.2147\/JIR.S344521","article-title":"Clenbuterol, a selective \u03b22-adrenergic receptor agonist, inhibits or limits post-stroke pneumonia, but increases infarct volume in MCAO mice","volume":"15","author":"Xu","year":"2022","journal-title":"J Inflammation Res"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.111.000633","article-title":"Simvastatin attenuates stroke-induced splenic atrophy and lung susceptibility to spontaneous bacterial infection in mice","volume":"44","author":"Jin","year":"2013","journal-title":"Stroke"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202206432","article-title":"Bone marrow mesenchymal stem cell-derived dermcidin-containing migrasomes enhance LC3-associated phagocytosis of pulmonary macrophages and protect against post-stroke pneumonia","volume":"10","author":"Li","year":"2023","journal-title":"Adv Sci (Weinh)"},{"key":"B52","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.brainresbull.2021.06.021","article-title":"Orexin-A inhibits cerebral ischaemic inflammatory injury mediated by the nuclear factor-\u03baB signalling pathway and alleviates stroke-induced immunodepression in mice","volume":"174","author":"Zhao","year":"2021","journal-title":"Brain Res Bull"},{"key":"B53","doi-asserted-by":"publisher","first-page":"577568","DOI":"10.1016\/j.jneuroim.2021.577568","article-title":"Efficacy and safety of intratracheal IFN-\u03b3 treatment to reverse stroke-induced susceptibility to pulmonary bacterial infections","volume":"355","author":"Jagdmann","year":"2021","journal-title":"J Neuroimmunology"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2018.03.005","article-title":"Immunomodulatory treatment with systemic GM-CSF augments pulmonary immune responses and improves neurological outcome after experimental stroke","volume":"321","author":"Dames","year":"2018","journal-title":"J Neuroimmunology"},{"key":"B55","doi-asserted-by":"publisher","first-page":"e121560","DOI":"10.1172\/jci.insight.121560","article-title":"IL-33 modulates inflammatory brain injury but exacerbates systemic immunosuppression following ischemic stroke","volume":"3","author":"Zhang","year":"2018","journal-title":"JCI Insight"},{"key":"B56","doi-asserted-by":"publisher","first-page":"6922","DOI":"10.1038\/s41598-019-43364-7","article-title":"IL-37 increases in patients after ischemic stroke and protects from inflammatory brain injury, motor impairment and lung infection in mice","volume":"9","author":"Zhang","year":"2019","journal-title":"Sci Rep"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13553","article-title":"Treatment with IgM-enriched intravenous immunoglobulins enhances clearance of stroke-associated bacterial lung infection","volume":"167","author":"McCulloch","year":"2022","journal-title":"Immunology"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.888684","article-title":"Herb formula (GCis) prevents pulmonary infection secondary to intracerebral hemorrhage by enhancing peripheral immunity and intestinal mucosal immune barrier","volume":"13","author":"Miao","year":"2022","journal-title":"Front Pharmacol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"156756","DOI":"10.1016\/j.phymed.2025.156756","article-title":"Tongfu Xingshen capsule alleviates stroke-associated pneumonia-induced multiple organ injuries by modulating the gut microbiota and sphingolipid metabolism","volume":"142","author":"Wang","year":"2025","journal-title":"Phytomedicine: Int J Phytotherapy Phytopharmacology"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000063373.70993.CD","article-title":"Nosocomial pneumonia after acute stroke: implications for neurological intensive care medicine","volume":"34","author":"Hilker","year":"2003","journal-title":"Stroke"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1159\/000111499","article-title":"Cellular immunodepression preceding infectious complications after acute ischemic stroke in humans","volume":"25","author":"Haeusler","year":"2008","journal-title":"Cerebrovascular Dis"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.06.014","article-title":"Harms and benefits of lymphocyte subpopulations in patients with acute stroke","volume":"158","author":"Urra","year":"2009","journal-title":"Neuroscience"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.107.493635","article-title":"Analysis of lymphocyte subsets in patients with stroke and their influence on infection after stroke","volume":"39","author":"Vogelgesang","year":"2008","journal-title":"Stroke"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.12659\/msm.890844","article-title":"Role of the sympathetic nervous system and spleen in experimental stroke-induced immunodepression","volume":"20","author":"Yan","year":"2014","journal-title":"Med Sci Monitor: Int Med J Exp Clin Res"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.12201","article-title":"Changes in the cellular immune system and circulating inflammatory markers of stroke patients","volume":"8","author":"Jiang","year":"2017","journal-title":"Oncotarget"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2016.03.034","article-title":"Increased expression of microRNA-21 in peripheral blood mediates the down-regulation of IFN-\u03b3 and increases the prevalence of stroke-associated infection","volume":"366","author":"Lin","year":"2016","journal-title":"J Neurol Sci"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.11.6523","article-title":"Splenic atrophy in experimental stroke is accompanied by increased regulatory T cells and circulating macrophages","volume":"176","author":"Offner","year":"2006","journal-title":"J Immunol (Baltimore Md 1950)"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2016.08.012","article-title":"The volume of the spleen and its correlates after acute stroke","volume":"25","author":"Chiu","year":"2016","journal-title":"J Stroke Cerebrovascular Diseases: Off J Natl Stroke Assoc"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1111\/ijs.12022","article-title":"Changes in spleen size in patients with acute ischemic stroke: a pilot observational study","volume":"8","author":"Sahota","year":"2012","journal-title":"Int J Stroke: Off J Int Stroke Soc"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.114.008260","article-title":"\u03b2-Blockers, pneumonia, and outcome after ischemic stroke: evidence from virtual international stroke trials archive","volume":"46","author":"Sykora","year":"2015","journal-title":"Stroke"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116836","article-title":"Effect of beta-blocker therapy on the risk of infections and death after acute stroke--a historical cohort study","volume":"10","author":"Maier","year":"2015","journal-title":"PloS One"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0196174","article-title":"Influence of beta-blocker therapy on the risk of infections and death in patients at high risk for stroke induced immunodepression","volume":"13","author":"Maier","year":"2018","journal-title":"PloS One"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1159\/000450926","article-title":"Pre-stroke use of beta-blockers does not lower post-stroke infection rate: an exploratory analysis of the preventive antibiotics in stroke study","volume":"42","author":"Westendorp","year":"2016","journal-title":"Cerebrovasc Dis"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1038\/35013070","article-title":"Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin","volume":"405","author":"Borovikova","year":"2000","journal-title":"Nature"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1172\/jci30555","article-title":"Physiology and immunology of the cholinergic antiinflammatory pathway","volume":"117","author":"Tracey","year":"2007","journal-title":"J Clin Invest"},{"key":"B76","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1186\/s12883-019-1481-5","article-title":"Augmentation of peripheral lymphocyte-derived cholinergic activity in patients with acute ischemic stroke","volume":"19","author":"Yuan","year":"2019","journal-title":"BMC Neurol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1359-19.2019","article-title":"Short-chain fatty acids improve poststroke recovery via immunological mechanisms","volume":"40","author":"Sadler","year":"2019","journal-title":"J Neurosci"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.316448","article-title":"Gut microbiota-derived short-chain fatty acids promote poststroke recovery in aged mice","volume":"127","author":"Lee","year":"2020","journal-title":"Circ Res"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.869846","article-title":"Gut microbiota composition reflects disease progression, severity and outcome, and dysfunctional immune responses in patients with hypertensive intracerebral hemorrhage","volume":"13","author":"Luo","year":"2022","journal-title":"Front Immunol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2019.104403","article-title":"Transplantation of fecal microbiota rich in short chain fatty acids and butyric acid treat cerebral ischemic stroke by regulating gut microbiota","volume":"148","author":"Chen","year":"2019","journal-title":"Pharmacol Res"},{"key":"B81","doi-asserted-by":"publisher","first-page":"872","DOI":"10.3390\/jcm9030872","article-title":"Early post-stroke infections are associated with an impaired function of neutrophil granulocytes","volume":"9","author":"van Gemmeren","year":"2020","journal-title":"J Clin Med"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385","article-title":"Neutrophil extracellular traps kill bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1159\/000111499","article-title":"Cellular immunodepression preceding infectious complications after acute ischemic stroke in humans","volume":"25","author":"Haeusler","year":"2007","journal-title":"Cerebrovasc Dis"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.493635","article-title":"Analysis of lymphocyte subsets in patients with stroke and their influence on infection after stroke","volume":"39","author":"Vogelgesang","year":"2007","journal-title":"Stroke"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00755","article-title":"Blood glutamate levels are closely related to acute lung injury and prognosis after stroke","volume":"8","author":"Bai","year":"2018","journal-title":"Front Neurol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-016-1899-8","article-title":"Blocking sympathetic nervous system reverses partially stroke-induced immunosuppression but does not aggravate functional outcome after experimental stroke in rats","volume":"41","author":"Deng","year":"2016","journal-title":"Neurochem Res"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2015.103","article-title":"Arginase I release from activated neutrophils induces peripheral immunosuppression in a murine model of stroke","volume":"35","author":"Sippel","year":"2015","journal-title":"J Cereb Blood Flow Metab"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118474","article-title":"Buyang huanwu decoction alleviates stroke-induced immunosuppression in MCAO mice by reducing splenic T cell apoptosis triggered by AIM2 inflammasome","volume":"333","author":"Fu","year":"2024","journal-title":"J Ethnopharmacol"},{"key":"B89","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.exger.2017.10.024","article-title":"Age and immunity: what is \"immunosenescence\"","volume":"105","author":"Pawelec","year":"2018","journal-title":"Exp Gerontology"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.5vmr0118-021rr","article-title":"Obesity and type 2 diabetes mellitus drive immune dysfunction, infection development, and sepsis mortality","volume":"104","author":"Frydrych","year":"2018","journal-title":"J Leukoc Biol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.116.303604","article-title":"The sympathetic nervous system alterations in human hypertension","volume":"116","author":"Grassi","year":"2015","journal-title":"Circ Res"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1856660\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:36:33Z","timestamp":1784180193000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1856660\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,16]]},"references-count":91,"alternative-id":["10.3389\/fimmu.2026.1856660"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1856660","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,16]]},"article-number":"1856660"}}