Department of Immunology and Molecular Biology, University of Gondar, Gondar, Ethiopia.
Ethiopian Public Health Institute, Addis Ababa, Ethiopia.
PLoS Negl Trop Dis. 2021 Mar 2;15(3):e0009194. doi: 10.1371/journal.pntd.0009194. eCollection 2021 Mar.
Both Mycobacterium tuberculosis infection and helminths may affect innate immune mechanisms such as differential effects on monocytes towards the non-classical and intermediate subsets that favor bacterial persistence. Our aim, was to investigate helminth species specific effects on the frequency and functional activity of monocyte subsets in patients with active tuberculosis and healthy subjects. HIV-negative patients with active pulmonary tuberculosis (PTB) and community controls (CCs) in Gondar, Ethiopia were screened for helminth infection by stool microscopy. Flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and ex vivo stimulation with purified protein derivative (PPD) and helminth antigens were used to characterize the distribution of monocyte subsets and their function. A total of 74 PTB patients and 57 CCs with and without helminth infection were included. Non-classical monocytes were increased in PTB patients with Ascaris and hookworm infection but not in Schistosoma-infected patients. Ascaris had the strongest effect in increasing the frequency of non-classical monocytes in both PTB patients and CCs, whereas PTB without helminth infection did not affect the frequency of monocyte subsets. There was a helminth specific increase in the frequency of TNF-α producing non-classical monocytes in hookworm infected PTB patients, both with and without PPD-stimulation. Low-to-intermediate TB disease severity associated with increased frequency of non-classical monocytes only for helminth-positive PTB patients, and the frequency of TNF-α producing monocytes were significantly higher in intermediate and non-classical monocytes of helminth positive PTB patients with an intermediate disease score. Helminth infection affected the frequency of monocyte subsets and function both in TB patients and controls which was helminth species dependent in TB patients. The clinical role of this potential immunomodulatory effect needs further study and may affect the response and protection to tuberculosis in areas where helminth infections are endemic.
结核分枝杆菌感染和寄生虫可能会影响先天免疫机制，例如对单核细胞向非经典和中间亚群的分化产生不同影响，从而有利于细菌的持续存在。我们的目的是研究寄生虫种类特异性对活动性肺结核患者和健康对照者单核细胞亚群频率和功能活性的影响。在埃塞俄比亚贡德尔，对患有活动性肺结核（PTB）的 HIV 阴性患者和社区对照者（CC）进行粪便显微镜检查，以筛查寄生虫感染。使用流式细胞术分析外周血单核细胞（PBMC）和纯化蛋白衍生物（PPD）和寄生虫抗原的体外刺激，以表征单核细胞亚群的分布及其功能。共纳入了 74 例 PTB 患者和 57 例有和无寄生虫感染的 CC。非经典单核细胞在感染蛔虫和钩虫的 PTB 患者中增加，但在感染血吸虫的患者中则没有。蛔虫对 PTB 患者和 CC 中非经典单核细胞频率的增加作用最强，而无寄生虫感染的 PTB 则不会影响单核细胞亚群的频率。在钩虫感染的 PTB 患者中，无论是在 PPD 刺激下还是不刺激下，寄生虫特异性地增加了 TNF-α 产生的非经典单核细胞的频率。低至中度 TB 疾病严重程度与非经典单核细胞频率增加相关，仅在寄生虫阳性的 PTB 患者中，而中间和非经典单核细胞中 TNF-α 产生的单核细胞在中间疾病评分的寄生虫阳性 PTB 患者中显著更高。寄生虫感染影响了 TB 患者和对照者单核细胞亚群的频率和功能，而在 TB 患者中则依赖于寄生虫的种类。这种潜在的免疫调节作用的临床作用需要进一步研究，并且可能会影响寄生虫流行地区对结核病的反应和保护。
