Emily Miltenberger, Janitzio Guzmán, Rodaba Rahim, Miranda Yu, Michelle Makiya, Perla Adames Castillo, Soo Ching Lee, Theodore E Nash, Amy D Klion, Thomas B Nutman, Elise M O'Connell
{"title":"蛛网膜下腔神经囊虫病患者中枢神经系统嗜酸性粒细胞的募集和激活。","authors":"Emily Miltenberger, Janitzio Guzmán, Rodaba Rahim, Miranda Yu, Michelle Makiya, Perla Adames Castillo, Soo Ching Lee, Theodore E Nash, Amy D Klion, Thomas B Nutman, Elise M O'Connell","doi":"10.1186/s12974-025-03540-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objectives: </strong>Subarachnoid neurocysticercosis (SANCC) is the most severe manifestation of neurocysticercosis. Most complications (communicating hydrocephalus, ischemic stroke, aneurysm, and subarachnoid hemorrhage) are due to inflammation localized to the central nervous system (CNS). The role of eosinophils in the inflammation associated with SANCC has not been previously studied.</p><p><strong>Methods: </strong>Cryopreserved CSF collected as part of a clinical trial for neurocysticercosis (NCC) were assessed for analytes associated with eosinophil activation and recruitment using multiplex bead assays in both subjects with SANCC (n = 28) and in NCC-negative controls (n = 26). The SANCC patients underwent chart review for extraction of clinical variables as well as grouping by disease severity to identify analytes that may be associated with the development of more severe symptoms of SANCC.</p><p><strong>Results: </strong>Eosinophil granule proteins (EGPs - ECP, EDN, and EPO), markers of eosinophil activation, were elevated in the CSF of SANCC patients compared to controls. Moreover, the eosinophil-associated cytokines/chemokines IL-5, IL-13, IL-18, CCL24/eotaxin-2, and CCL26/eotaxin-3 were also significantly elevated in the CSF of SANCC patients compared to controls. In those for whom there were paired specimens (n = 13) from baseline and following cure, there was a significant reduction in these cytokines/chemokines (except CCL26/eotaxin-3). The percentage of CSF white blood cells that were eosinophils was positively correlated with EDN, EPO, IL-5, IL-13, CCL24, CCL26, CCL8, CCL13, and CCL5/RANTES, as well as the time it took to achieve biomarker cure. When SANCC patients were subdivided between those with severe disease and those with non-severe disease, the levels of eosinophil cationic protein (ECP), the CCR3 ligands (CCL7 and CCL5), CCL4, IL-18, and IL-1RA discriminated clearly between these 2 groups. DISCUSSION: These data provide evidence for eosinophil recruitment and activation in the subarachnoid space in patients with SANCC, as well as for a potential role of eosinophils in driving inflammation-associated complications.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"22 1","pages":"215"},"PeriodicalIF":10.1000,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465403/pdf/","citationCount":"0","resultStr":"{\"title\":\"Eosinophil recruitment and activation in the central nervous system of patients with subarachnoid neurocysticercosis.\",\"authors\":\"Emily Miltenberger, Janitzio Guzmán, Rodaba Rahim, Miranda Yu, Michelle Makiya, Perla Adames Castillo, Soo Ching Lee, Theodore E Nash, Amy D Klion, Thomas B Nutman, Elise M O'Connell\",\"doi\":\"10.1186/s12974-025-03540-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objectives: </strong>Subarachnoid neurocysticercosis (SANCC) is the most severe manifestation of neurocysticercosis. Most complications (communicating hydrocephalus, ischemic stroke, aneurysm, and subarachnoid hemorrhage) are due to inflammation localized to the central nervous system (CNS). The role of eosinophils in the inflammation associated with SANCC has not been previously studied.</p><p><strong>Methods: </strong>Cryopreserved CSF collected as part of a clinical trial for neurocysticercosis (NCC) were assessed for analytes associated with eosinophil activation and recruitment using multiplex bead assays in both subjects with SANCC (n = 28) and in NCC-negative controls (n = 26). The SANCC patients underwent chart review for extraction of clinical variables as well as grouping by disease severity to identify analytes that may be associated with the development of more severe symptoms of SANCC.</p><p><strong>Results: </strong>Eosinophil granule proteins (EGPs - ECP, EDN, and EPO), markers of eosinophil activation, were elevated in the CSF of SANCC patients compared to controls. Moreover, the eosinophil-associated cytokines/chemokines IL-5, IL-13, IL-18, CCL24/eotaxin-2, and CCL26/eotaxin-3 were also significantly elevated in the CSF of SANCC patients compared to controls. In those for whom there were paired specimens (n = 13) from baseline and following cure, there was a significant reduction in these cytokines/chemokines (except CCL26/eotaxin-3). The percentage of CSF white blood cells that were eosinophils was positively correlated with EDN, EPO, IL-5, IL-13, CCL24, CCL26, CCL8, CCL13, and CCL5/RANTES, as well as the time it took to achieve biomarker cure. When SANCC patients were subdivided between those with severe disease and those with non-severe disease, the levels of eosinophil cationic protein (ECP), the CCR3 ligands (CCL7 and CCL5), CCL4, IL-18, and IL-1RA discriminated clearly between these 2 groups. DISCUSSION: These data provide evidence for eosinophil recruitment and activation in the subarachnoid space in patients with SANCC, as well as for a potential role of eosinophils in driving inflammation-associated complications.</p>\",\"PeriodicalId\":16577,\"journal\":{\"name\":\"Journal of Neuroinflammation\",\"volume\":\"22 1\",\"pages\":\"215\"},\"PeriodicalIF\":10.1000,\"publicationDate\":\"2025-09-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465403/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Neuroinflammation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12974-025-03540-1\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neuroinflammation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12974-025-03540-1","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Eosinophil recruitment and activation in the central nervous system of patients with subarachnoid neurocysticercosis.
Background and objectives: Subarachnoid neurocysticercosis (SANCC) is the most severe manifestation of neurocysticercosis. Most complications (communicating hydrocephalus, ischemic stroke, aneurysm, and subarachnoid hemorrhage) are due to inflammation localized to the central nervous system (CNS). The role of eosinophils in the inflammation associated with SANCC has not been previously studied.
Methods: Cryopreserved CSF collected as part of a clinical trial for neurocysticercosis (NCC) were assessed for analytes associated with eosinophil activation and recruitment using multiplex bead assays in both subjects with SANCC (n = 28) and in NCC-negative controls (n = 26). The SANCC patients underwent chart review for extraction of clinical variables as well as grouping by disease severity to identify analytes that may be associated with the development of more severe symptoms of SANCC.
Results: Eosinophil granule proteins (EGPs - ECP, EDN, and EPO), markers of eosinophil activation, were elevated in the CSF of SANCC patients compared to controls. Moreover, the eosinophil-associated cytokines/chemokines IL-5, IL-13, IL-18, CCL24/eotaxin-2, and CCL26/eotaxin-3 were also significantly elevated in the CSF of SANCC patients compared to controls. In those for whom there were paired specimens (n = 13) from baseline and following cure, there was a significant reduction in these cytokines/chemokines (except CCL26/eotaxin-3). The percentage of CSF white blood cells that were eosinophils was positively correlated with EDN, EPO, IL-5, IL-13, CCL24, CCL26, CCL8, CCL13, and CCL5/RANTES, as well as the time it took to achieve biomarker cure. When SANCC patients were subdivided between those with severe disease and those with non-severe disease, the levels of eosinophil cationic protein (ECP), the CCR3 ligands (CCL7 and CCL5), CCL4, IL-18, and IL-1RA discriminated clearly between these 2 groups. DISCUSSION: These data provide evidence for eosinophil recruitment and activation in the subarachnoid space in patients with SANCC, as well as for a potential role of eosinophils in driving inflammation-associated complications.
期刊介绍:
The Journal of Neuroinflammation is a peer-reviewed, open access publication that emphasizes the interaction between the immune system, particularly the innate immune system, and the nervous system. It covers various aspects, including the involvement of CNS immune mediators like microglia and astrocytes, the cytokines and chemokines they produce, and the influence of peripheral neuro-immune interactions, T cells, monocytes, complement proteins, acute phase proteins, oxidative injury, and related molecular processes.
Neuroinflammation is a rapidly expanding field that has significantly enhanced our knowledge of chronic neurological diseases. It attracts researchers from diverse disciplines such as pathology, biochemistry, molecular biology, genetics, clinical medicine, and epidemiology. Substantial contributions to this field have been made through studies involving populations, patients, postmortem tissues, animal models, and in vitro systems.
The Journal of Neuroinflammation consolidates research that centers around common pathogenic processes. It serves as a platform for integrative reviews and commentaries in this field.