Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Italy.
Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Parasit Vectors. 2020 Oct 15;13(1):515. doi: 10.1186/s13071-020-04391-w.
Strongyloidiasis caused by Strongyloides stercoralis is a soil-transmitted helminthiasis affecting an estimated 370 million people and considered one of the most neglected tropical diseases. Although mostly distributed in tropical and subtropical areas, autochthonous infections have also been documented in north-eastern Italy, even though the transmission presumably stopped decades ago. Because of its peculiar auto-infective cycle, strongyloidiasis can persist lifelong, but the pathophysiological mechanisms associated with the maintenance of such a chronic infection are yet to be fully deciphered.
Serum levels of 23 immune factors were retrospectively assessed in a subgroup of participants in a randomised clinical trial for the treatment of strongyloidiasis (Strong Treat). Here we included Italian subjects born between 1931 and 1964 and diagnosed with strongyloidiasis between 2013 and 2017 (Ss, n = 32). Serum samples obtained before (BT) and 6 months (6M AT) after ivermectin treatment, as well as from age- and gender-matched uninfected controls (CTRL, n = 34) were analysed.
The assessed immune factors showed a general reduced concertation in Ss patients and a lack of association with eosinophilia. In our cohort, we did not observe the classical shift towards a type 2 immune response, since Th1 and Th2 cytokines were mostly unaltered. Instead, we observed chemokines as particularly affected by the presence of the parasite, since IL-8, CCL3, CCL4 and CCL5 were significantly reduced in concentration in Ss subjects compared to CTRL, suggesting that immune cell recruitment to the infection site might be dampened in these patients. This observation was further sustained by a significant increase of CCL4, CCL5 and CCL11 concentrations 6M AT. A significant raised systemic concentration of three growth factors, bFGF, PDGF-BB and IL-7 (haematopoietic growth factor) was also observed post-treatment, indicating a potential involvement in restoring tissue integrity and homeostasis following parasite elimination.
These preliminary data suggest that, in order to survive for such a long period, S. stercoralis might suppress host responses that could otherwise result in its ejection. Our results offer novel insights in the potential mechanisms of disease tolerance that might take place during this chronic infection, including a potential T-cell hypo-responsiveness and a role for chemokines.
由旋毛线蚓（Strongyloides stercoralis）引起的旋毛虫病是一种土壤传播的蠕虫病，影响估计有 3.7 亿人，被认为是最被忽视的热带病之一。尽管旋毛虫病主要分布在热带和亚热带地区，但在意大利东北部也有本地感染的记录，尽管据推测几十年前传播就已经停止。由于其独特的自体感染循环，旋毛虫病可以持续终生，但与维持这种慢性感染相关的病理生理机制仍有待完全破译。
我们回顾性地评估了一项旋毛虫病治疗随机临床试验（Strong Treat）中一个亚组参与者的 23 种免疫因子的血清水平。在这里，我们纳入了 1931 年至 1964 年期间出生并于 2013 年至 2017 年期间被诊断为旋毛虫病的意大利受试者（Ss，n=32）。分析了他们接受伊维菌素治疗前（BT）和 6 个月（6M AT）后的血清样本，以及年龄和性别匹配的未感染对照组（CTRL，n=34）的血清样本。
评估的免疫因子在 Ss 患者中普遍表现出浓度降低，并且与嗜酸性粒细胞增多无关。在我们的队列中，我们没有观察到向 2 型免疫反应的经典转变，因为 Th1 和 Th2 细胞因子大多没有改变。相反，我们观察到趋化因子受到寄生虫的特别影响，因为与 CTRL 相比，IL-8、CCL3、CCL4 和 CCL5 的浓度在 Ss 患者中显著降低，这表明在这些患者中，免疫细胞向感染部位的募集可能受到抑制。这一观察结果进一步得到了 6M AT 时 CCL4、CCL5 和 CCL11 浓度显著增加的支持。还观察到三种生长因子（碱性成纤维细胞生长因子（bFGF）、血小板衍生生长因子-BB（PDGF-BB）和白细胞介素-7（造血生长因子））的系统浓度显著升高，这表明在寄生虫消除后，可能参与了组织完整性和体内平衡的恢复。
这些初步数据表明，为了能够长期存活，旋毛线蚓可能会抑制宿主的反应，否则宿主的反应可能会导致旋毛线蚓被排出。我们的结果为慢性感染过程中可能发生的疾病耐受的潜在机制提供了新的见解，包括潜在的 T 细胞低反应性和趋化因子的作用。
