Instituto de Medicina Tropical 'Alexander von Humboldt', Facultad de Medicina "Alberto Hurtado", Universidad Peruana Cayetano Heredia, Lima, Peru.
Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch at Galveston, Texas, United States of America.
PLoS Negl Trop Dis. 2019 Jun 6;13(6):e0007415. doi: 10.1371/journal.pntd.0007415. eCollection 2019 Jun.
Strongyloides stercoralis is an intestinal nematode unique in its ability to replicate in the human host, allowing ongoing cycles of autoinfection, persisting for decades within the same host. Although usually asymptomatic, overwhelming infections can occur in Strongyloides and HTLV-1 co-infected individuals (SS/HTLV-1). Regulatory T cells (Tregs) are able to blunt specific Th2 responses necessary to control the parasite. We previously reported that peripheral blood Tregs are increased in SS/HTLV-1 and correlate with low Th2 responses. We hypothesized that Tregs are also increased at the site of infection in duodenal mucosa.
Paraffin embedded duodenal biopsies were obtained from 10 SS/HTLV-1 patients, 3 controls with non-parasitic chronic duodenitis, and 2 healthy controls. Immunohistochemistry was performed using monoclonal antibodies against human CD3, CD8, IgE and FoxP3. The number of cells were counted using a conventional light microscope. The number of CD3+, CD8+, FoxP3+ and IgE positive cells per 0.35 mm2 was measured using ImagePro Plus software comparing areas adjacent or distant from parasite material.
In patients with SS/HTLV-1, T lymphocyte counts and CD8+ cells were lower in areas adjacent to the parasite compared to non-adjacent areas (CD3+: adjacent: 6.5 [Interquartile range (IQR: 2.8-12.3)]; non-adjacent: 24.5 [IQR: 20.9-34.4]; Mann-Whitney p = 0.0003; CD8+: adjacent: 4.5 [IQR: 2.3-11.8]; non-adjacent: 21 [IQR: 15.3-42.9]; Mann-Whitney p = 0.0011). Tregs cells in the intestines (FoxP3+ expressing cells) were increased in patients with SS/HTLV-1 compared with patients with chronic duodenitis (SS/HTLV-1: 1.5 [IQR: 0.7-2.3]; duodenitis controls: 0 [range 0-0.7]; healthy controls: 0; Mann-Whitney p = 0.034). There was also a trend towards fewer eosinophils adjacent to the parasites. Among SS/HTLV-1 patients the number of IgE expressing cells was increased for in areas not adjacent to the parasite compared to non-adjacent areas (ANOVA, p = 0.001).
Our data shows increased Treg cell numbers localized adjacent to the parasites in the duodenum SS/HTLV-1 patients. In addition, other T lymphocytes and IgE expressing cells were decreased adjacent to the parasites, suggesting an important role for Tregs in down-regulating local parasite effector responses.
旋毛虫是一种独特的肠道线虫，能够在人类宿主中复制，从而允许持续的自体感染循环，在同一宿主中持续数十年。虽然通常无症状，但在旋毛虫和 HTLV-1 合并感染的个体（SS/HTLV-1）中可能会发生严重感染。调节性 T 细胞（Tregs）能够抑制控制寄生虫所需的特定 Th2 反应。我们之前报道过，SS/HTLV-1 患者外周血 Tregs 增加，并与 Th2 反应降低相关。我们假设 Tregs 在十二指肠黏膜的感染部位也增加。
从 10 例 SS/HTLV-1 患者、3 例非寄生虫性慢性十二指肠炎对照和 2 例健康对照中获得石蜡包埋的十二指肠活检。使用针对人 CD3、CD8、IgE 和 FoxP3 的单克隆抗体进行免疫组织化学染色。使用常规显微镜计数细胞数。使用 ImagePro Plus 软件测量每 0.35mm2 的 CD3+、CD8+、FoxP3+和 IgE 阳性细胞数，比较寄生虫物质附近和不附近的区域。
在 SS/HTLV-1 患者中，与不相邻区域相比，寄生虫附近的 T 淋巴细胞计数和 CD8+细胞减少（CD3+：相邻：6.5 [四分位距（IQR：2.8-12.3）]；不相邻：24.5 [IQR：20.9-34.4]；Mann-Whitney p=0.0003；CD8+：相邻：4.5 [IQR：2.3-11.8]；不相邻：21 [IQR：15.3-42.9]；Mann-Whitney p=0.0011）。与慢性十二指肠炎患者相比，SS/HTLV-1 患者肠道中的 Treg 细胞（表达 FoxP3 的细胞）增加（SS/HTLV-1：1.5 [IQR：0.7-2.3]；十二指肠炎对照：0 [范围 0-0.7]；健康对照：0；Mann-Whitney p=0.034）。寄生虫附近的嗜酸性粒细胞也有减少的趋势。在 SS/HTLV-1 患者中，与不相邻区域相比，寄生虫不相邻区域 IgE 表达细胞增加（ANOVA，p=0.001）。
我们的数据显示，SS/HTLV-1 患者十二指肠内寄生虫附近的 Treg 细胞数量增加。此外，寄生虫附近的其他 T 淋巴细胞和 IgE 表达细胞减少，表明 Tregs 在下调局部寄生虫效应反应中起重要作用。
