Division of Infectious Diseases and Tropical Medicine, University Hospital, LMU Munich Germany.
National Institute for Medical Research (NIMR)-Mbeya Medical Research Center (MMRC), Mbeya, Tanzania.
PLoS Negl Trop Dis. 2019 Aug 19;13(8):e0007623. doi: 10.1371/journal.pntd.0007623. eCollection 2019 Aug.
Susceptibility to HIV has been linked to systemic CD4+ T cell activation in cohorts of seronegative individuals with high HIV-exposure risk. We recently described an increased risk of HIV transmission in individuals infected with Wuchereria bancrofti, the causative agent for lymphatic filariasis, in a prospective cohort study. However, the reason for this phenomenon needs further investigation.
METHODOLOGY/PRINCIPAL FINDINGS: Two-hundred and thirty-five HIV negative adults were tested using Trop Bio ELISA for detection of W. bancrofti infection and Kato Katz urine filtration and stool based RT-PCR for detection of soil transmitted helminths and schistosomiasis. FACS analysis of the fresh peripheral whole blood was used to measure T cell activation markers (HLA-DR, CD38), differentiation markers (CD45, CD27), markers for regulatory T cells (FoxP3, CD25) and the HIV entry receptor CCR5. Frequencies of activated HLA-DRpos CD4 T cells were significantly increased in subjects with W. bancrofti infection (n = 33 median: 10.71%) compared to subjects without any helminth infection (n = 42, median 6.97%, p = 0.011) or those with other helminths (Schistosoma haematobium, S. mansoni, Trichuris trichiura, Ascaris lumbricoides, hookworm) (n = 151, median 7.38%, p = 0.009). Similarly, a significant increase in HLA-DRposCD38pos CD4 T cells and effector memory cells CD4 T cells (CD45ROposCD27neg) was observed in filarial infected participants. Multivariable analyses further confirmed a link between W. bancrofti infection and systemic activation of CD4 T cells independent of age, fever, gender or other helminth infections.
CONCLUSIONS/SIGNIFICANCE: W. bancrofti infection is linked to systemic CD4 T cell activation, which may contribute to the increased susceptibility of W. bancrofti infected individuals to HIV infection.
在高 HIV 暴露风险的血清阴性个体队列中，HIV 易感性与全身 CD4+T 细胞活化有关。我们最近在一项前瞻性队列研究中描述了感染班氏丝虫（引起淋巴丝虫病的病原体）的个体中 HIV 传播风险增加。然而，这种现象的原因需要进一步研究。
方法/主要发现：235 名 HIV 阴性成年人接受了 Trop Bio ELISA 检测，以检测是否存在班氏丝虫感染，并用加藤氏尿液过滤和粪便 RT-PCR 检测是否存在土壤传播的蠕虫和血吸虫病。使用新鲜外周全血的 FACS 分析来测量 T 细胞活化标志物（HLA-DR、CD38）、分化标志物（CD45、CD27）、调节性 T 细胞标志物（FoxP3、CD25）和 HIV 进入受体 CCR5。与无任何蠕虫感染（n=42，中位数 6.97%，p=0.011）或其他蠕虫（埃及血吸虫、曼氏血吸虫、鞭虫、蛔虫、钩虫）感染（n=151，中位数 7.38%，p=0.009）的个体相比，班氏丝虫感染者（n=33，中位数 10.71%）的 HLA-DRpos CD4 T 细胞的频率显著增加。同样，在感染丝虫的参与者中也观察到 HLA-DRpos CD38pos CD4 T 细胞和效应记忆细胞 CD4 T 细胞（CD45ROpos CD27neg）的显著增加。多变量分析进一步证实，班氏丝虫感染与 CD4 T 细胞的全身活化有关，而与年龄、发热、性别或其他蠕虫感染无关。
结论/意义：班氏丝虫感染与全身 CD4 T 细胞活化有关，这可能导致感染班氏丝虫的个体对 HIV 感染的易感性增加。
