Asymptomatic Helminth Infection in Active Tuberculosis Is Associated with Increased Regulatory and Th-2 Responses and a Lower Sputum Smear Positivity.
Asymptomatic Helminth Infection in Active Tuberculosis Is Associated with Increased Regulatory and Th-2 Responses and a Lower Sputum Smear Positivity.
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DOI：
10.1371/journal.pntd.0003994
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发表时间：
2015-08
影响因子：
3.8
通讯作者：
Schön T
中科院分区：
文献类型：
--
作者：
Abate E;Belayneh M;Idh J;Diro E;Elias D;Britton S;Aseffa A;Stendahl O;Schön T
肠道蠕虫感染对活动性结核病（TB）感染的临床表现和免疫反应的影响尚不清楚。我们的目的是研究无症状肠道蠕虫感染是否会改变活动性结核病患者的临床体征和症状以及细胞介导的免疫反应。在埃塞俄比亚西北部招募了连续的新诊断结核病患者和健康社区对照（cc）。分析tb评分、体重指数和粪便样本。使用流式细胞术和ELISPOT分别分析HIV阴性结核患者（HIV-/TB）和CCs细胞的调节性t细胞（Tregs）和细胞因子反应。未感染HIV的结核病患者（Helm+/HIV-/TB）的蠕虫合并感染比例显著高于HIV阴性的CCs患者(40% （121/306)vs 28% (85/306), p = 0.003）。与Helm-/HIV-/TB患者相比，Helm+/HIV-/TB患者IL-5分泌细胞显著增加(37 SFU (IQR: 13-103) vs 2 SFU (1-50)；P = 0.02, n = 30)。同样，绝对Tregs水平(9.4 (3.2-16.7)cells/μl vs . 2.4 (1.1-4.0) cells/μl；p = 0.041)和IL-10分泌细胞(65 SFU (7-196) vs 1 SFU (0-31))；p = 0.014)，与Helm-/HIV-/TB患者相比，Helm+/HIV-/TB患者的死亡率显著高于Helm-/HIV-/TB患者。在一项多变量分析中，抗酸杆菌痰涂片阳性率较低、体温较低和嗜酸性粒细胞增多与结核病患者的寄生虫感染独立相关。无症状蠕虫感染与调节性t细胞和th2型反应增加以及痰涂片阳性率降低有关。需要进一步研究寄生虫感染对结核病患者的临床和免疫学影响。蠕虫感染对慢性传染病（如结核病）的影响值得进一步研究。在高流行地区的临床实地研究中，关于寄生虫合并感染对结核病临床和免疫学结果的影响的数据有限。我们试图在一项随机临床试验中解决其中的一些问题，以调查阿苯达唑治疗对寄生虫合并感染结核病患者的影响。在本研究中，我们重点研究了寄生虫感染对结核病的临床和免疫学作用。我们发现，伴发的无症状蠕虫感染深刻影响了TB患者的免疫表型，其免疫反应强烈倾向于Th2型，如调节性T细胞以及IL-5和IL-10分泌细胞的增加。此外，寄生虫合并感染与痰涂片阳性率显著降低相关，而痰涂片阳性率与寄生虫阳性结核病患者的卵载量相关。寄生虫感染的作用是否会对活动性结核病的诊断和治疗产生影响还有待进一步研究。
The impact of intestinal helminth infection on the clinical presentation and immune response during active tuberculosis (TB) infection is not well characterized. Our aim was to investigate whether asymptomatic intestinal helminth infection alters the clinical signs and symptoms as well as the cell mediated immune responses in patients with active TB. Consecutive, newly diagnosed TB patients and healthy community controls (CCs) were recruited in North-west Ethiopia. TB-score, body mass index and stool samples were analyzed. Cells from HIV-negative TB patients (HIV-/TB) and from CCs were analyzed for regulatory T-cells (Tregs) and cytokine responses using flow cytometry and ELISPOT, respectively. A significantly higher ratio of helminth co-infection was observed in TB patients without HIV (Helm+/HIV-/TB) compared to HIV negative CCs, (40% (121/306) versus 28% (85/306), p = 0.003). Helm+/HIV-/TB patients showed significantly increased IL-5 secreting cells compared to Helm-/HIV-/TB (37 SFU (IQR:13–103) versus 2 SFU (1–50); p = 0.02, n = 30). Likewise, levels of absolute Tregs (9.4 (3.2–16.7) cells/μl versus 2.4 (1.1–4.0) cells/μl; p = 0.041) and IL-10 secreting cells (65 SFU (7–196) versus 1 SFU (0–31); p = 0.014) were significantly higher in Helm+/HIV-/TB patients compared to Helm-/HIV-/TB patients. In a multivariate analysis, a lower rate of sputum smear positivity for acid fast bacilli, lower body temperature, and eosinophilia were independently associated with helminth infection in TB patients. Asymptomatic helminth infection is associated with increased regulatory T-cell and Th2-type responses and a lower rate of sputum smear positivity. Further studies are warranted to investigate the clinical and immunological impact of helminth infection in TB patients. The effects of helminth infection on chronic infectious diseases such as tuberculosis (TB) merit further characterization. There is limited data regarding the impact of helminth co-infection on clinical and immunological outcomes of TB from clinical field studies in high endemic areas. We tried to address some of these issues in a randomized clinical trial in order to investigate the impact of albendazole treatment on helminth co-infected TB patients. In the present study we focused on the clinical and immunological effects of helminth infection on TB. We found that concomitant asymptomatic helminth infection profoundly affects the immune phenotype of TB patients with a strong leaning towards Th2 types of immune response such as increased regulatory T cells as well as IL-5 and IL-10 secreting cells. Furthermore, helminth co-infection was associated with a significantly lower ratio of sputum smear positivity which correlated to the egg load in helminth positive TB patients. Whether the effect of helminth infection may have an impact on the diagnosis and treatment of active TB remains to be further investigated.