Chemokine and Cytokine Cascade Caused by Skewing of the Th1-Th2 Balance Is Associated with High Intracranial Pressure in HIV-Associated Cryptococcal Meningitis

Xu, Lijun; Guo, Yongzheng; Zhao, Yizhou; Xu, Yufan; Peng, Xiuming; Yang, Zongxing; Tao, Ran; Huang, Ying; Xu, Yan; Chen, Yaokai; Zhu, Bin

doi:10.1155/2019/2053958

Cited by 16 publications

(12 citation statements)

References 34 publications

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“…Our present study was coincident with our previous study, showing that Th1 cytokines (IL-12p70, TNF-β and TNF-α), Th2 cytokines (IL-5) and CD40L together contribute to HCM [11]. Th1 cytokine expression is an immune response to Cryptococcus infection and an over-response of Th1 cytokines is associated with extensive inflammation in Cryptococcus infection [22].…”

Section: Discussionsupporting

confidence: 91%

“…Furthermore, the CSF cytokine profiles predicted immune reconstitution inflammatory syndrome (IRIS) and even mortality in HCM patients [4]. Our study also showed that chemokine and cytokine cascades caused by the skewing of the T helper type (Th)1–Th2 balance are associated with severity in HCM patients [11]. Inflammatory mediators in the CSF are attracting increasing attention, and play a critical role in HTBM [12].…”

Section: Introductionmentioning

confidence: 86%

“…Pre‐treatment CSF samples were collected between January 2013 and December 2016 and frozen at −80°C for subsequent analysis. According to our pre‐test results and a previous study [11], the following cytokines/chemokines were assayed in the CSF samples of all patients: interleukin (IL)‐1β, IL‐1Rα, IL‐4, IL‐5, IL‐6, IL‐8 [chemokine (C‐X‐C motif) ligand 8], IL‐10, IL‐12p40, IL‐12p70, CD40L, interferon (IFN)‐γ, IFN‐α2, tumor necrosis factor (TNF)‐α, TNF‐β, Fms‐like tyrosine kinase 3‐ligand (Flt3L), regulated upon activation, normal T cell expressed and secreted (RANTES) [chemokine (C‐C motif) ligand 5], granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and monocyte chemotactic protein‐1 (MCP‐1). The Luminex multianalyte platform (Luminex) and Milliplex ® map (cat.…”

Section: Methodsmentioning

confidence: 97%

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Differences in cytokine and chemokine profiles in cerebrospinal fluid caused by the etiology of cryptococcal meningitis and tuberculous meningitis in HIV patients

Zheng

et al. 2021

Clinical and Experimental Immunology

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The roles of cytokines and chemokines in HIV-associated cryptococcal meningitis (HCM) and HIV-associated tuberculous meningitis (HTBM) are debatable. In sum, 34 HIV-infected patients without meningitis, 44 HCM patients and 27 HTBM patients were enrolled for study. The concentrations of 22 cytokines/chemokines in cerebrospinal fluid (CSF) were assayed at admission. Principal component analysis (PCA), Pearson's and logistic regression analyses were used to assess the role of cytokines/chemokines in HCM and HTBM. We found the levels of T helper (Th)17, Th1 [interleukin (IL)-12p40, interferon (IFN)-γ, tumor necrosis factor (TNF)-α and TNF-β and Th2 (IL-2/4/5/6/10)] cytokines were elevated in patients with meningitis compared with those in HIV-infected patients without central nervous system (CNS) infection. Furthermore, the IL-1Ra, IL-12p40, IL-17α and monocyte chemotactic protein-1 (MCP-1) levels were higher in HCM patients, while the IFN-γ, regulated upon activation, normal T cell expressed and secreted (RANTES) and interferoninducible protein-10 (IP)-10 levels were higher in HTBM patients. Elevated CSF concentrations of IL-17a, TNF-β, IL-5, IL-12p40 and IL-1Rα were closely related to meningitis, but elevated IP-10, MCP-1, RANTES and IFN-γ levels and CSF white blood cells (WBCs) were protective factors against HCM. Our study suggested that HIV-infected patients with low CSF WBCs have a high risk of HCM. Th1, Th2 and Th17 cytokines/chemokines mediate differences in the pathogenesis of HCM and TBM. Overexpressed proinflammatory MCP-1, RANTES, IFN-γ and IP-10 in CSF are protective factors against HCM but not HTBM.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 86%

Section: Methodsmentioning

confidence: 97%

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Differences in cytokine and chemokine profiles in cerebrospinal fluid caused by the etiology of cryptococcal meningitis and tuberculous meningitis in HIV patients

Zheng

et al. 2021

Clinical and Experimental Immunology

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“…Cryptococcus spp. Isolates (8,14,(34)(35)(36)(37)(38). Genetic and environmental factors contribute to the variation in the melanin production of C. neoformans (39,40), which is under complex cellular regulation (40,41).…”

Section: Discussionmentioning

confidence: 99%

FasterCryptococcusmelanization increases virulence in experimental and human cryptococcosis

Sousa

Júnior

Frazão

et al. 2020

Preprint

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Cryptococcus spp. are important human pathogens responsible for about 180,000 deaths per year. Studying their virulence attributes can lead to better cryptococcosis prevention and treatment. In this work, we systematically investigated virulence attributes of Cryptococcus spp. clinical isolates and correlated them with patient data. We collected 66 C. neoformans and 19 C. gattii isolates from Brazilian patients and analyzed multiple phenotypes related with their capsule, production of laccase, melanin and extracellular vesicles. We also tested their virulence in Galleria mellonella and ability to evade macrophage LC3-associated phagocytosis (LAP). All phenotypes analyzed varied widely among the isolates, but C. neoformans isolates tended to melanize faster and more intensely and produce thinner capsules in comparison with C. gattii. We also observed correlations that match previous studies, such as that between secreted laccase – but not total melanin production – and disease outcome in patients. The most striking results, though, came from our measurements of Cryptococcus colony melanization kinetics, which followed a sigmoidal curve for most isolates. Faster melanization correlated positively with LAP evasion, virulence in G. mellonella and worse prognosis in humans. These results suggest that the speed of melanization, more than the total amount of melanin Cryptococcus spp. produces, is crucial for virulence.Graphical abstract

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“…On the opposite, Th2 cytokines act as down-regulators of the cellular immune response, inhibit T cell proliferation and are associated with impaired infection control and poor prognosis [ 15 , 24 ]. Xu et al found that [ 25 ], HIV + CM+ patients had higher levels of CSF cytokines and chemokines than HIV-CM- patients, Th1 cytokines (such as TNF-α, IFN-γ and IL-12), Th2 cytokines (such as IL-4, IL-5, IL-6 and IL-12) and macrophage cytokines (such as IL-8 and CCL2) were particular high indicated the unbalance of Th1-Th2 cytokines in CSF. Most of our results were consistent with the previous study, but we found IL-4 in CSF of HIV + CM+ patients were lower than that of HIV-CM- patients.…”

Section: Discussionmentioning

confidence: 99%

A preliminary study on the characteristics of Th1/Th2 immune response in cerebrospinal fluid of AIDS patients with cryptococcal meningitis

Zhu

et al. 2021

BMC Infect Dis

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Background Cryptococcal Meningitis (CM) is a common opportunistic infection in the late stage of acquired immunodeficiency syndrome (AIDS). Despite the wide use of effective antiretroviral and antifungal therapy in AIDS patients, CM is still a major morbidity and mortality cause. Understanding the immune response in cryptococcal infection may help to improve the treatment strategies. Methods We established a prospective cohort of twelve AIDS patients with CM (HIV + CM+) admitted to the hospital from 2019 to 2020. All patients were examined at the baseline, 2 weeks, and 4 weeks thereafter. The level of 19 cytokines in cerebrospinal fluid (CSF) were recorded to analyze the characteristics and dynamic changes of Th1/Th2 immune response. Meanwhile, six AIDS patients without CM (HIV + CM-) and seventeen healthy subjects (HIV-CM-) were included as control groups for CSF assessment. Results The HIV+ CM+ group had higher CSF IFN-γ, TNF-α, IL-6, IL-7, IL-8, IL-10, IL-12 (P40), IL-15, IL-18, CCL2 levels but lower IL-4 when compared with the HIV-CM- group at baseline. And they also had a higher level of IL-12 (P40) and IL-17A compared with HIV + CM- patients. Except one patient dropped out of the study, eleven HIV + CM+ patients received induction antifungal therapy and regular CSF testing, and the mortality rate was 9.1% (1/11) and 18.2% (2/11) respectively at week 2 and week 4. Compared with baseline CSF cytokines, IL-2, IL-13, IL-17A, and VEGF-A decreased in week 2, and the VEGF-A levels further decreased in week 4. But there was no difference in the levels of all cytokines between survivors and the dead. Conclusion No evidence of Th1/Th2 imbalance was found in AIDS patients with CM. However, the CSF cytokine network may provide new clues for the treatment of AIDS patients with CM. Trial registration This trial was prospectively registered in 2019.7.16. The registered number is ChiCTR1900024565.

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Chemokine and Cytokine Cascade Caused by Skewing of the Th1-Th2 Balance Is Associated with High Intracranial Pressure in HIV-Associated Cryptococcal Meningitis

Cited by 16 publications

References 34 publications

Differences in cytokine and chemokine profiles in cerebrospinal fluid caused by the etiology of cryptococcal meningitis and tuberculous meningitis in HIV patients

Differences in cytokine and chemokine profiles in cerebrospinal fluid caused by the etiology of cryptococcal meningitis and tuberculous meningitis in HIV patients

FasterCryptococcusmelanization increases virulence in experimental and human cryptococcosis

A preliminary study on the characteristics of Th1/Th2 immune response in cerebrospinal fluid of AIDS patients with cryptococcal meningitis

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