I.I. Mechnikov Institute of Vaccine and Sera, 105064 Moscow, Russia.
N.F. Gamaleya National Research Center for Epidemiology and Microbiology, 123098 Moscow, Russia.
Viruses. 2023 Jun 6;15(6):1330. doi: 10.3390/v15061330.
HIV-1 infection is characterized by aberrant immune activation, and infection with by an unbalanced production of proinflammatory cytokines. The expression of these cytokines in HIV-1/TB coinfection is still understudied. Here, we aimed to compare the production of proinflammatory cytokines in drug-naive patients coinfected with HIV-1 and (HIV/TB) compared to patients with respective monoinfections. Plasma samples of patients with HIV/TB coinfection ( = 36), HIV-1 monoinfection ( = 36), and TB monoinfection ( = 35) and healthy donors ( = 36) were examined for the levels of eight proinflammatory cytokines. Their levels were significantly increased in all patient groups compared to healthy donors. At the same time, a drastic decrease in the plasma levels of IFN-γ, TNF-α, Il-1β, IL-15, and IL-17 was detected in patients with HIV/TB coinfection compared to patients with HIV-1 or TB monoinfections. The plasma levels of IL-17 characterized the TB severity: in HIV/TB-coinfected patients with disseminated TB, plasma levels of IL-17 were eight times lower than in patients with less severe TB forms (infiltrative TB or TB of intrathoracic lymph nodes; < 0.0001). At the same time, HIV/TB-coinfected patients had increased plasma levels of IL-8, IL-12, and IL-18, with the levels of IL-8 correlating with mortality ( < 0.0001). Thus, on the contrary to the patients with HIV-1 or TB monoinfections, HIV/TB-coinfected patients had suppressed production of most of the proinflammatory cytokines associated with antimicrobial immune response, specifically of T-cells involved in the containment of both infections. At the same time, they demonstrated an expansion of proinflammatory cytokines known to originate from both hematopoietic and nonhematopoietic cells, and manifest tissue inflammation. In HIV-1/TB coinfection, this leads to the disruption of granuloma formation, contributing to bacterial dissemination and enhancing morbidity and mortality.
HIV-1 感染的特征是免疫激活异常，而 感染则会导致促炎细胞因子的失衡产生。HIV-1/TB 合并感染中这些细胞因子的表达仍在研究中。在这里，我们旨在比较未经药物治疗的 HIV-1 和 （HIV/TB）合并感染患者与各自单感染患者的促炎细胞因子产生情况。我们检测了 HIV/TB 合并感染患者（n=36）、HIV-1 单感染患者（n=36）、TB 单感染患者（n=35）和健康供者（n=36）的血浆样本中八种促炎细胞因子的水平。与健康供者相比，所有患者组的这些细胞因子水平均显著升高。同时，我们发现与 HIV-1 或 TB 单感染患者相比，HIV/TB 合并感染患者的血浆中 IFN-γ、TNF-α、IL-1β、IL-15 和 IL-17 水平显著降低。血浆中 IL-17 水平可反映 TB 的严重程度：在 HIV/TB 合并感染中，广泛型 TB 患者的血浆中 IL-17 水平比非广泛型 TB 患者（浸润型 TB 或胸内淋巴结 TB； < 0.0001）低八倍。同时，HIV/TB 合并感染患者的血浆中 IL-8、IL-12 和 IL-18 水平升高，IL-8 水平与死亡率相关（ < 0.0001）。因此，与 HIV-1 或 TB 单感染患者相反，HIV/TB 合并感染患者的大多数与抗微生物免疫反应相关的促炎细胞因子产生受到抑制，特别是与控制两种感染相关的 T 细胞。同时，他们表现出促炎细胞因子的扩张，这些细胞因子已知来源于造血细胞和非造血细胞，并表现出组织炎症。在 HIV-1/TB 合并感染中，这会导致肉芽肿形成的破坏，导致细菌播散并增加发病率和死亡率。
