Aira Naomi, Andersson Anna-Maria, Singh Susmita K, McKay Derek M, Blomgran Robert
Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
Gastrointestinal Research Group, Department of Physiology and Pharmacology, Snyder Institute for Chronic Disease, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
PLoS Negl Trop Dis. 2017 Feb 13;11(2):e0005390. doi: 10.1371/journal.pntd.0005390. eCollection 2017 Feb.
In countries with a high prevalence of tuberculosis there is high coincident of helminth infections that might worsen disease outcome. While Mycobacterium tuberculosis (Mtb) gives rise to a pro-inflammatory Th1 response, a Th2 response is typical of helminth infections. A strong Th2 response has been associated with decreased protection against tuberculosis.
We investigated the direct effect of helminth-derived antigens on human macrophages, hypothesizing that helminths would render macrophages less capable of controlling Mtb. Measuring cytokine output, macrophage surface markers with flow cytometry, and assessing bacterial replication and phagosomal maturation revealed that antigens from different species of helminth directly affect macrophage responses to Mtb. Antigens from the tapeworm Hymenolepis diminuta and the nematode Trichuris muris caused an anti-inflammatory response with M2-type polarization, reduced macrophage phagosome maturation and ability to activate T cells, along with increased Mtb burden, especially in T. muris exposed cells which also induced the highest IL-10 production upon co-infection. However, antigens from the trematode Schistosoma mansoni had the opposite effect causing a decrease in IL-10 production, M1-type polarization and increased control of Mtb.
We conclude that, independent of any adaptive immune response, infection with helminth parasites, in a species-specific manner can influence the outcome of tuberculosis by either enhancing or diminishing the bactericidal function of macrophages.
在结核病高流行国家，蠕虫感染的发生率也很高，这可能会使疾病预后恶化。结核分枝杆菌（Mtb）会引发促炎性Th1反应，而Th2反应是蠕虫感染的典型特征。强烈的Th2反应与结核病防护能力下降有关。
我们研究了蠕虫衍生抗原对人巨噬细胞的直接影响，推测蠕虫会使巨噬细胞控制Mtb的能力降低。通过测量细胞因子输出、用流式细胞术检测巨噬细胞表面标志物以及评估细菌复制和吞噬体成熟，发现来自不同种类蠕虫的抗原会直接影响巨噬细胞对Mtb的反应。来自微小膜壳绦虫和鼠鞭虫的抗原会引发具有M2型极化的抗炎反应，降低巨噬细胞吞噬体成熟度和激活T细胞的能力，同时增加Mtb负荷，尤其是在感染鼠鞭虫的细胞中，共感染时这些细胞还会诱导产生最高水平的IL-10。然而，来自曼氏血吸虫的抗原则具有相反的效果，会导致IL-10产生减少、M1型极化以及对Mtb的控制增加。
我们得出结论，独立于任何适应性免疫反应，蠕虫寄生虫感染能够以物种特异性方式，通过增强或减弱巨噬细胞的杀菌功能来影响结核病的结局。
