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

Abstract

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.

The predictive value of TNF family for pulmonary tuberculosis: a pooled causal effect analysis of multiple datasets

“…Additionally, higher levels of TNF were detected in peripheral blood mononuclear cells of patients newly diagnosed with TB compared to those with chronic refractory TB ( 20 – 22 ). Compared to Human Immunodeficiency Virus(HIV)–infected patients without central nervous system involvement, HIV-associated tuberculous meningitis patients exhibited elevated levels of T-helper factor (Th) 17, TNF-α, and LT ( 23 ). In the study conducted by Jing Wei et al., the Kyoto Genomic Encyclopedia and single gene enrichment analysis of peripheral blood mononuclear cells from the Asian population of Mtb-Ag stimulated and control samples revealed a significant enrichment of the TNF signaling pathway, which is closely associated with tuberculosis.…”

“…These findings substantiate the efficacy of LT as a predictive factor for PTB. Moreover, among individuals co-infected with HIV and TB, the utilization of inflammatory biomarker signatures successfully identified those at the highest risk for developing PTB ( 23 ). These inflammatory biomarkers reflect numerous activations of innate immunity and increased Th1 responses, which are associated with the immune response to MTB.…”

Interactions between CNS and immune cells in tuberculous meningitis

“…Xu et al. found that the expression levels of Th1, Th2, Th 17, TNF-α, and TNF-β were elevated in TBM patients compared to those without the CNS infections in HIV-infected persons ( 122 ). Moreover, the expression levels of IFN-γ, regulated upon activation normal T cells expressed and presumably secreted (RANTES) and interferon-inducible protein (IP-10) in TBM patients were higher than in non-TBM with HIV infection.…”

“…Another report indicated that IL-2-positive T lymphocytes in the CSF of TBM patients can produce specific and reactive antigen when stimulated with IL-2, antigen-presenting cells (APC), or Muromonab CD3 (OKT3) antibody (121). Xu et al found that the expression levels of Th1, Th2, Th 17, TNF-a, and TNF-b were elevated in TBM patients compared to those without the CNS infections in HIV-infected persons (122). Moreover, the expression levels of IFN-g, regulated upon activation normal T cells expressed and presumably secreted (RANTES) and interferon-inducible protein (IP-10) in TBM patients were higher than in non-TBM with HIV infection.…”

MRI advances in the imaging diagnosis of tuberculous meningitis: opportunities and innovations

“…Intriguingly, these symptoms parallel those of bacterial meningitis and viral meningitis, further complicating the timely diagnostic process. In advanced disease states, the onset of neurological complications sharply exacerbates both mortality and the likelihood of lasting disability linked to TBM ( Roca et al, 2008 ; Török, 2015 ; Mezochow et al, 2017 ; Kumar et al, 2021 ; Xu et al, 2021 ). Hence, early, precise, and expedient diagnostic and therapeutic interventions are crucial to reducing the mortality associated with this condition.…”