Mpaka-Mbatha Miranda N, Naidoo Pragalathan, Bhengu Khethiwe N, Islam Md Mazharul, Singh Ravesh, Nembe-Mafa Nomzamo, Mkhize-Kwitshana Zilungile L
Department of Medical Microbiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, Nelson R. Mandela Medical School Campus, University of KwaZulu-Natal, Durban 4001, South Africa.
Division of Research Capacity Development (RCD), South African Medical Research Council (SAMRC), Tygerberg, Cape Town 7505, South Africa.
Diagnostics (Basel). 2023 Jul 25;13(15):2475. doi: 10.3390/diagnostics13152475.
Intestinal helminth parasites are potent stimulators of T helper type 2 (Th2) and regulatory Th3 anti-inflammatory immune responses, while human immunodeficiency virus (HIV) infections are activators of predominantly T helper type 1(Th1) pro-inflammatory responses. Studies investigating the immune profiles of individuals coinfected with helminths and HIV are scarce. Although it is well known that helminths cause a type 2 immune response during the chronic stage of infection that is characterised by Th2 cell differentiation, eosinophil recruitment, and alternative macrophage activation, the immune mechanisms that regulate tissue damage at the time of parasite invasion are poorly understood.
The aim of the study was to determine the cytokine gene expression profiles during HIV and helminth coinfection in underprivileged South African adults living in a peri-urban area with poor sanitary conditions and a lack of clean water supply.
Study participants ( = 164) were subdivided into uninfected controls, HIV-infected, helminth-infected, and HIV and helminth-coinfected groups. The Kato-Katz and Mini Parasep techniques and -specific Immunoglobulin E (IgE) and Immunoglobulin G4 (IgG4) levels were used to detect helminth infections. Participants' HIV status was determined using two HIV1/2 antibody test kits. RNA was isolated from white blood cells for cytokine (Th1-, Th2-, and Th17-related) and transcription factor gene expression profiling using real-time PCR.
Multivariate regression data were adjusted for age, gender, BMI, antiretroviral treatment (ART), and nutritional supplement intake. The HIV and helminth-coinfected group had significantly higher tumour necrosis factor alpha () (adjusted β = 0.53, = 0.036), interleukin 2 ) (adjusted β = 6.48, = 0.008), and interleukin 17 () (adjusted β = 1.16, = 0.001) levels and lower GATA binding protein 3 ) levels (adjusted β = -0.77, = 0.018) compared to the uninfected controls. No statistical significance was noted for Th2-related cytokines.
The coinfected group had higher proinflammatory Th1- and Th17-related cytokine gene expression profiles compared to the uninfected controls. The findings suggest that pro-inflammatory responses are elevated during coinfection, which supports the hypothesis that helminths have a deleterious effect on HIV immune responses.
肠道蠕虫寄生虫是2型辅助性T细胞(Th2)和调节性Th3抗炎免疫反应的强效刺激物,而人类免疫缺陷病毒(HIV)感染主要激活1型辅助性T细胞(Th1)促炎反应。关于同时感染蠕虫和HIV的个体免疫特征的研究很少。虽然众所周知,蠕虫在感染的慢性阶段会引发以Th2细胞分化、嗜酸性粒细胞募集和替代性巨噬细胞激活为特征的2型免疫反应,但在寄生虫入侵时调节组织损伤的免疫机制却知之甚少。
本研究的目的是确定生活在卫生条件差且缺乏清洁水源的城郊地区的贫困南非成年人在同时感染HIV和蠕虫期间的细胞因子基因表达谱。
研究参与者(n = 164)被分为未感染对照组、HIV感染组、蠕虫感染组以及HIV和蠕虫同时感染组。采用加藤厚涂片法和微型寄生虫分离技术以及特异性免疫球蛋白E(IgE)和免疫球蛋白G4(IgG4)水平来检测蠕虫感染。使用两种HIV1/2抗体检测试剂盒确定参与者的HIV感染状况。从白细胞中分离RNA,用于通过实时聚合酶链反应进行细胞因子(与Th1、Th2和Th17相关)和转录因子基因表达谱分析。
多变量回归数据针对年龄、性别、体重指数、抗逆转录病毒治疗(ART)和营养补充剂摄入量进行了调整。与未感染对照组相比,HIV和蠕虫同时感染组的肿瘤坏死因子α(TNF-α)(调整后β = 0.53,P = 0.036)、白细胞介素2(IL-2)(调整后β = 6.48,P = 0.008)和白细胞介素17(IL-17)(调整后β = 1.16,P = 0.001)水平显著更高,而GATA结合蛋白3(GATA-3)水平更低(调整后β = -0.77,P = 0.018)。与Th2相关的细胞因子未观察到统计学显著性差异。
与未感染对照组相比,同时感染组具有更高的促炎Th1和Th17相关细胞因子基因表达谱。这些发现表明,同时感染期间促炎反应升高,这支持了蠕虫对HIV免疫反应有有害影响的假设。