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

Abstract

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.

Cryptococcal Immune Reconstitution Inflammatory Syndrome: From Clinical Studies to Animal Experiments

“…Compared to healthy individuals, HIV/AIDS patients with cryptococcal meningoencephalitis displayed higher CSF levels of IFN-γ, TNF-α, IL-6, IL-7, IL-8, IL-10, IL-12p40, IL-15, IL-18, and CCL2 [37]. They also had higher levels of CSF IL-12p40 and IL-17A compared with HIV/AIDS patients without co-infection of C. neoformans, suggesting inflammation of the CNS during cryptococcal meningoencephalitis [37]. Inflammatory responses are thought to play a prominent role in the eradication of cryptococcal infections in the CNS [38].…”

Clinical characteristics and prognostic factors of 60 patients with acquired immune deficiency syndrome combined with Cryptococcus neoformans

“…The prognostic criteria for AIDS combined with CM were as follows [11]: (1) Clinically cured -after treatment, the patient's clinical symptoms disappeared, cerebrospinal fluid pressure and routine biochemical examination results returned to normal, no Cryptococcus was found in three consecutive cerebrospinal fluid, blood and bone marrow fungal cultures (every 7 d) and the patient was stable for more than 4 weeks; (2) Improved -clinical symptoms and signs improved significantly, cerebrospinal fluid pressure was normal and the results of the cerebrospinal fluid biochemical examination and bacterial culture were occasionally positive; and (3) Ineffective -after treatment, the patient's clinical symptoms and signs did not improve significantly or worsened and the patient was either discharged or died. The 60 patients in the study were divided into Group A (32 patients with CM) and Group B (28 patients without CM).…”

Neglected mycobiome in HIV infection: Alterations, common fungal diseases and antifungal immunity

“…CM can occur following primary lung infection or by reactivation and dissemination of latent pulmonary infection in the setting of cell-mediated immunodeficiency when CD4 + T-cell counts are <100 cells/μl in the late-stages of HIV-infection ( 98 ). Previous studies have shown that CD4 + T cells possibly mediate protective host immunity against cryptococcal via production of Th1-type cytokine responses, including IL-2, IL-12, tumor necrosis factor alpha (TNF-α), and IFN-γ, which play an essential role in recruitment of lymphocytes and phagocytes to clear the infection ( 99 , 100 ). Higher levels of IFN-γ in cerebrospinal fluid (CSF) are associated with a faster rate of fungal clearance and lower fungal burdens ( 101 , 102 ).…”