Damane Botle Precious, Mulaudzi Thanyani Victor, Kader Sayed Shakeel, Naidoo Pragalathan, Dlamini Zodwa, Mkhize-Kwitshana Zilungile Lynette
Department of Surgery, Steve Biko Academic Hospital, University of Pretoria, Hatfield 0028, South Africa.
Department of Medical Microbiology, College of Health Sciences, School of Laboratory Medicine & Medical Sciences, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban 4041, South Africa.
Viruses. 2025 Mar 20;17(3):451. doi: 10.3390/v17030451.
South Africa has the highest HIV prevalence globally, often co-occurring with helminth infections in impoverished regions. The coexistence of these infections leads to immunological interactions, potentially enhancing oncogenesis by upregulating immune checkpoint molecules (ICs) among other effects. Notably, most ICs are overexpressed in cancer and correlated with its progression. Helminth infections trigger Th2-type immunity, increasing immunosuppressive M2 macrophages, regulatory T cells, and associated IC molecules. PD-L2 is reported to contribute to Th2-type immunity induced by helminth infections. Similarly, TIM-3, elevated during chronic viral infections, induces a similar immunosuppressive profile. CTLA-4 and PD-1 impact T-cell function by interacting with CD28, crucial for T-cell function. CD28 is downregulated in chronic infections and cancer. This study investigated the impact of HIV-helminth co-infection on co-stimulatory and co-inhibitory molecule profiles associated with antitumor immunity. Using 78 serum samples collected from March 2020 to May 2021, participants were categorized into uninfected control (no HIV and helminth infections), HIV-infected, helminth-infected, and HIV-helminth co-infected groups. Multiplex immune regulatory molecule assay analysis was conducted. The data were analyzed using multivariate regression analysis and adjusted for confounders (age, gender, BMI, ART, supplements, and other chronic diseases). The uninfected control group was used as the baseline reference group for analysis. HIV-infected individuals had higher PD-1 (adjusted β = 0.12, = 0.034) and TIM-3 (adjusted β = 23.15, = 0.052) levels, with the latter showing a trend toward significance. However, lower CD28 levels (adjusted β = -651.95, = 0.010) were observed. Helminth-infected individuals had higher TIM-3 levels (adjusted β = 20.98, = 0.020). The co-infected group had higher PD-1 (unadjusted β = 0.18, = 0.0046) and PD-L2 (adjusted β = 7.95, = 0.033) levels. A significant decrease in CD28 profile was observed across all infected groups: HIV-infected (adjusted β = -651.95, = 0.010), helminth-infected (adjusted β = -674.32, = 0.001), and co-infected (adjusted β = -671.55, = 0.044). The results suggest that HIV-helminth co-infections alter immune checkpoint markers, potentially increasing cancer risk by promoting an immunosuppressive microenvironment that hinders anti-cancer immunity. CD28's downregulation underscores immune inefficiency in chronic diseases. Addressing these co-infections is crucial for improving HIV care and potentially reducing cancer risks through targeted strategies.
南非是全球艾滋病毒感染率最高的国家，在贫困地区，艾滋病毒感染常常与蠕虫感染同时发生。这些感染的共存会导致免疫相互作用，除其他影响外，还可能通过上调免疫检查点分子（ICs）来增强肿瘤发生。值得注意的是，大多数ICs在癌症中过度表达，并与其进展相关。蠕虫感染会引发Th2型免疫，增加免疫抑制性M2巨噬细胞、调节性T细胞及相关的IC分子。据报道，PD-L2有助于蠕虫感染诱导的Th2型免疫。同样，在慢性病毒感染期间升高的TIM-3也会诱导类似的免疫抑制状态。CTLA-4和PD-1通过与对T细胞功能至关重要的CD28相互作用来影响T细胞功能。CD28在慢性感染和癌症中表达下调。本研究调查了艾滋病毒与蠕虫合并感染对抗肿瘤免疫相关的共刺激和共抑制分子谱的影响。使用2020年3月至2021年5月收集的78份血清样本，将参与者分为未感染对照组（无艾滋病毒和蠕虫感染）、艾滋病毒感染组、蠕虫感染组和艾滋病毒与蠕虫合并感染组。进行了多重免疫调节分子分析。使用多元回归分析对数据进行分析，并对混杂因素（年龄、性别、体重指数、抗逆转录病毒治疗、补充剂和其他慢性病）进行校正。将未感染对照组用作分析的基线参考组。艾滋病毒感染者的PD-1（校正β = 0.12，P = 0.034）和TIM-
