{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T06:30:31Z","timestamp":1764916231380,"version":"3.46.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cytokines in the serum and cerebrospinal fluid (CSF) are critical to the pathogenesis of HIV-associated cryptococcal meningitis (HCM). Previous studies focused on baseline cytokine levels, but changes during antifungal therapy are underexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Twenty-three patients with a first episode of HCM were prospectively followed to evaluate immune cell and cytokine dynamics during antifungal treatment therapy. Clinical features and laboratory data were systematically collected, and principal component and correlation analyses were performed to identify immune factors associated with HCM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Typical clinical manifestations include fever, headache, and nausea, among others. All patients presented severely low CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell counts and a notable reduction in CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Over 28 days of antifungal treatment, significant decreases in the CSF levels of IL-2 and IL-10 and the plasma levels of IL-10 and IL-4 were observed. The plasma TNF-\u03b1 concentration remained stable from days 1 to 14, followed by a marked increase on day 21. Plasma IFN-\u03b3 was negatively correlated with neutrophils (P = 0.04, r = -0.297), while IL-1\u03b2 was positively correlated with leukocytes (P = 0.0031, r = 0.4266), and IL-8 was negatively correlated with lymphocytes (P = 0.0074, r = 0.3901). No significant correlations were found between other factors and neutrophils, leukocytes, or lymphocytes (P &amp;gt; 0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Cytokines derived from innate immune cells play a central role in host defense against HIV-associated cryptococcal infections. The observed reductions in cytokine levels in both plasma and CSF after antifungal therapy provide new insights into the immune response in HCM, highlighting the dynamic interplay of immune factors during treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1691025","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T06:25:09Z","timestamp":1764915909000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cytokine dynamics in the blood and cerebrospinal fluid of HIV\/AIDS patients with cryptococcal meningitis receiving antifungal therapy"],"prefix":"10.3389","volume":"15","author":[{"given":"Rui","family":"Su","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuwei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chongxi","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuye","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingkui","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenghui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1111\/j.1469-0691.2011.03741.x","article-title":"Immunotherapy of cryptococcus infections","volume":"18","author":"Antachopoulos","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"B2","doi-asserted-by":"publisher","first-page":"6346","DOI":"10.4049\/jimmunol.174.10.6346","article-title":"Role of IFN-gamma in regulating T2 immunity and the development of alternatively activated macrophages during allergic bronchopulmonary mycosis","volume":"174","author":"Arora","year":"2005","journal-title":"J. Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1172\/JCI114265","article-title":"Neutrophil-activating peptide-1\/interleukin 8, a novel cytokine that activates neutrophils","volume":"84","author":"Baggiolini","year":"1989","journal-title":"J. Clin. Invest."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e1000384","DOI":"10.1371\/journal.pmed.1000384","article-title":"Clinical features and serum biomarkers in HIV immune reconstitution inflammatory syndrome after cryptococcal meningitis: a prospective cohort study","volume":"7","author":"Boulware","year":"2010","journal-title":"PloS Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1146\/annurev.immunol.021908.132612","article-title":"Immunological and inflammatory functions of the interleukin-1 family","volume":"27","author":"Dinarello","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"ofz205","DOI":"10.1093\/ofid\/ofz205","article-title":"Innate immunity acts as the major regulator in talaromyces marneffei coinfected AIDS patients: cytokine profile surveillance during initial 6-month antifungal therapy","volume":"6","author":"Dong","year":"2019","journal-title":"Open Forum Infect. Dis."},{"key":"B7","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.micpath.2016.06.008","article-title":"The comparison of Th1, Th2, Th9, Th17 and Th22 cytokine profiles in acute and chronic HIV-1 infection","volume":"97","author":"Gorenec","year":"2016","journal-title":"Microb. Pathog."},{"key":"B8","doi-asserted-by":"publisher","first-page":"774","DOI":"10.2353\/ajpath.2010.090634","article-title":"Pulmonary infection with an interferon-gamma-producing Cryptococcus neoformans strain results in classical macrophage activation and protection","volume":"176","author":"Hardison","year":"2010","journal-title":"Am. J. Pathol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1111\/j.1600-065X.2008.00707.x","article-title":"Regulation of interferon and Toll-like receptor signaling during macrophage activation by opposing feedforward and feedback inhibition mechanisms","volume":"226","author":"Hu","year":"2008","journal-title":"Immunol. Rev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1093\/cid\/cit794","article-title":"Determinants of mortality in a combined cohort of 501 patients with HIV-associated Cryptococcal meningitis: implications for improving outcomes","volume":"58","author":"Jarvis","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2119","DOI":"10.1097\/QAD.0b013e3282a4a64d","article-title":"HIV-associated cryptococcal meningitis","volume":"21","author":"Jarvis","year":"2007","journal-title":"AIDS"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e1004754","DOI":"10.1371\/journal.ppat.1004754","article-title":"Cerebrospinal fluid cytokine profiles predict risk of early mortality and immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis","volume":"11","author":"Jarvis","year":"2015","journal-title":"PloS Pathog."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1097\/QAD.0b013e3283536a93","article-title":"Adjunctive interferon-gamma immunotherapy for the treatment of HIV-associated cryptococcal meningitis: a randomized controlled trial","volume":"26","author":"Jarvis","year":"2012","journal-title":"AIDS"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1007\/s10096-011-1245-7","article-title":"The effect of the expression of virulence-associated DEAD-box RNA helicase mRNA on the imbalance of Th1-Th2 cytokines in the CSF of patients with Cryptococcus neoformans meningitis","volume":"30","author":"Jiang","year":"2011","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B15","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1046\/j.1365-2249.1996.14723.x","article-title":"IL-12 protects mice against pulmonary and disseminated infection caused by Cryptococcus neoformans","volume":"104","author":"Kawakami","year":"1996","journal-title":"Clin. Exp. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1002\/rmv.369","article-title":"The influence of cytokines, chemokines and their receptors on HIV-1 replication in monocytes and macrophages","volume":"13","author":"Kedzierska","year":"2003","journal-title":"Rev. Med. Virol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1097\/00002030-199709000-00005","article-title":"Demonstration of the Th1 to Th2 cytokine shift during the course of HIV-1 infection using cytoplasmic cytokine detection on single cell level by flow cytometry","volume":"11","author":"Klein","year":"1997","journal-title":"AIDS"},{"key":"B18","doi-asserted-by":"publisher","first-page":"3653","DOI":"10.4049\/jimmunol.163.7.3653","article-title":"TNF-alpha inhibits HIV-1 replication in peripheral blood monocytes and alveolar macrophages by inducing the production of RANTES and decreasing C-C chemokine receptor 5 (CCR5) expression","volume":"163","author":"Lane","year":"1999","journal-title":"J. Immunol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1093\/infdis\/jir507","article-title":"Immunologic failure despite suppressive antiretroviral therapy is related to activation and turnover of memory CD4 cells","volume":"204","author":"Lederman","year":"2011","journal-title":"J. Infect. Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1126\/science.1214935","article-title":"Disease tolerance as a defense strategy","volume":"335","author":"Medzhitov","year":"2012","journal-title":"Science"},{"key":"B21","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1097\/QCO.0000000000000224","article-title":"The\u00a0immunopathogenesis of cryptococcal immune reconstitution inflammatory\u00a0syndrome: understanding a conundrum","volume":"29","author":"Meya","year":"2016","journal-title":"Curr. Opin. Infect. Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e0120297","DOI":"10.1371\/journal.pone.0120297","article-title":"Cytokine profiles at admission can be related to outcome in AIDS patients with cryptococcal meningitis","volume":"10","author":"Mora","year":"2015","journal-title":"PloS One"},{"key":"B23","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1093\/intimm\/dxt003","article-title":"Abrogation of IL-4 receptor-alpha-dependent alternatively activated macrophages is sufficient to confer resistance against pulmonary cryptococcosis despite an ongoing T(h)2 response","volume":"25","author":"M\u00fcller","year":"2013","journal-title":"Int. Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1128\/IAI.01477-13","article-title":"Interleukin-17A enhances host defense against cryptococcal lung infection through effects mediated by leukocyte recruitment, activation, and gamma interferon production","volume":"82","author":"Murdock","year":"2014","journal-title":"Infect. Immun."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e01415","DOI":"10.1128\/mBio.01415-17","article-title":"CD4(+) T Cells Orchestrate Lethal Immune Pathology despite Fungal Clearance during Cryptococcus neoformans Meningoencephalitis","volume":"8","author":"Neal","year":"2017","journal-title":"mBio"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e02063","DOI":"10.1128\/mBio.02063-17","article-title":"Immune-mediated damage completes the parabola: cryptococcus neoformans pathogenesis can reflect the outcome of a weak or strong immune response","volume":"8","author":"Pirofski","year":"2017","journal-title":"mBio"},{"key":"B27","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/S1473-3099(17)30243-8","article-title":"Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis","volume":"17","author":"Rajasingham","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"B28","doi-asserted-by":"publisher","first-page":"8008","DOI":"10.1038\/srep08008","article-title":"Capsular polysaccharides from Cryptococcus neoformans modulate production of neutrophil extracellular traps (NETs) by human neutrophils","volume":"5","author":"Rocha","year":"2015","journal-title":"Sci. Rep."},{"key":"B29","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1002\/art.40055","article-title":"Cerebrospinal fluid cytokines correlate with aseptic meningitis and blood\u2013Brain barrier function in neonatal-onset multisystem inflammatory disease: central nervous system biomarkers in neonatal-onset multisystem inflammatory disease correlate with central nervous system inflammation","volume":"69","author":"Rodriguez-Smith","year":"2017","journal-title":"Arthritis Rheumatol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"565","DOI":"10.2217\/fmb.14.132","article-title":"Host immunity to Cryptococcus neoformans","volume":"10","author":"Rohatgi","year":"2015","journal-title":"Future Microbiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/nri2939","article-title":"Immunity to fungal infections","volume":"11","author":"Romani","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.2217\/fmb.12.102","article-title":"Mechanisms of infection by the human fungal pathogen Cryptococcus neoformans","volume":"7","author":"Sabiiti","year":"2012","journal-title":"Future Microbiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1189\/jlb.0603252","article-title":"Interferon-gamma: an overview of signals, mechanisms and functions","volume":"75","author":"Schroder","year":"2004","journal-title":"J. Leukoc. Biol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1097\/QAI.0000000000001382","article-title":"The CSF immune response in HIV-1-associated cryptococcal meningitis: macrophage activation, correlates of disease severity, and effect of antiretroviral therapy","volume":"75","author":"Scriven","year":"2017","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e1006207","DOI":"10.1371\/journal.ppat.1006207","article-title":"Immune correlates of HIV-associated cryptococcal meningitis","volume":"13","author":"Tenforde","year":"2017","journal-title":"PloS Pathog."},{"key":"B36","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/s41572-023-00472-z","article-title":"Cryptococcal meningitis","volume":"9","author":"Tugume","year":"2023","journal-title":"Nat. Rev. Dis. Primers"},{"key":"B37","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1189\/jlb.1002476","article-title":"The polysaccharide capsule of Cryptococcus neoformans interferes with human dendritic cell maturation and activation","volume":"74","author":"Vecchiarelli","year":"2003","journal-title":"J. Leukoc. Biol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e0144427","DOI":"10.1371\/journal.pone.0144427","article-title":"The role of cryptococcus in the immune system of pulmonary cryptococcosis patients","volume":"10","author":"Wang","year":"2015","journal-title":"PloS One"},{"key":"B39","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1016\/S1473-3099(17)30245-1","article-title":"The relentless march of cryptococcal meningitis","volume":"17","author":"Williamson","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"B40","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/nrneurol.2016.167","article-title":"Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy","volume":"13","author":"Williamson","year":"2017","journal-title":"Nat. Rev. Neurol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1128\/IAI.00274-06","article-title":"Protection against cryptococcosis by using a murine gamma interferon-producing Cryptococcus neoformans strain","volume":"75","author":"Wormley","year":"2007","journal-title":"Infect. Immun."},{"key":"B42","doi-asserted-by":"publisher","first-page":"e6854","DOI":"10.1371\/journal.pone.0006854","article-title":"Insights into the mechanisms of protective immunity against Cryptococcus neoformans infection using a mouse model of pulmonary cryptococcosis","volume":"4","author":"Wozniak","year":"2009","journal-title":"PloS One"},{"key":"B43","doi-asserted-by":"publisher","first-page":"2053958","DOI":"10.1155\/2019\/2053958","article-title":"Chemokine and cytokine cascade caused by skewing of the th1-th2 balance is associated with high intracranial pressure in HIV-associated cryptococcal meningitis","volume":"2019","author":"Xu","year":"2019","journal-title":"Mediators Inflammation"},{"key":"B44","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1177\/0961203316629556","article-title":"IL-6, IL-8, IP-10, MCP-1 and G-CSF are significantly increased in cerebrospinal fluid but not in sera of patients with central neuropsychiatric lupus erythematosus","volume":"25","author":"Yoshio","year":"2016","journal-title":"Lupus"},{"key":"B45","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s40249-023-01073-4","article-title":"Cryptococcus neoformans, a global threat to human health","volume":"12","author":"Zhao","year":"2023","journal-title":"Infect. Dis. Poverty"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1089\/aid.2014.0106","article-title":"The immune pathogenesis of immune reconstitution inflammatory syndrome associated with highly active antiretroviral therapy in AIDS","volume":"30","author":"Zheng","year":"2014","journal-title":"AIDS Res. Hum. Retroviruses"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1691025\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T06:25:10Z","timestamp":1764915910000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1691025\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,5]]},"references-count":46,"alternative-id":["10.3389\/fcimb.2025.1691025"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1691025","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,5]]},"article-number":"1691025"}}