Parasitic helminth infections in humans modulate Trefoil Factor levels in a manner dependent on the species of parasite and age of the host.
Parasitic helminth infections in humans modulate Trefoil Factor levels in a manner dependent on the species of parasite and age of the host.
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DOI：
10.1371/journal.pntd.0009550
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发表时间：
2021-10
影响因子：
3.8
通讯作者：
Herbert DR
中科院分区：
文献类型：
--
作者：
Adewale B;Heintz JR;Pastore CF;Rossi HL;Hung LY;Rahman N;Bethony J;Diemert D;Babatunde JA;Herbert DR
蠕虫感染，包括钩虫和血吸虫，可导致严重残疾和死亡。早期发现和预测预后的生物标志物有助于感染的管理和控制。虽然动物模型表明三叶因子家族蛋白(TFF2和TFF3)和白介素33(IL-33)驱动的2型免疫反应在钩虫感染背景下是组织修复和蠕虫清除的关键介质，但对于它们在人类蠕虫感染背景下是如何调节的知之甚少。我们检测了巴西钩虫和/或血吸虫感染患者血清中TFF2、TFF3和IL-33的水平，并将它们与地方性和非地方性对照进行了比较。TFF2在女性钩虫感染中特异性升高，而不是血吸虫或混合感染。这一升高与年龄相关，但与蠕虫负担无关。TFF3在血吸虫感染后升高，在女性中普遍升高。感染对IL-33无明显影响。为了确定这是否可能更广泛地适用于其他物种或地区，我们测量了感染血吸虫的尼日利亚学童的血清和尿液中的TFF和细胞因子水平(干扰素γ、肿瘤坏死因子α、IL-33、IL-13、IL-1β、IL-17A、IL-22和IL-10)。我们发现血清TFF2和TFF3水平因感染而降低，可能以一种年龄依赖的方式。血清中仅IL-10和IL-13显著升高，而尿液中干扰素-γ、肿瘤坏死因子-α、IL-13、IL-1β、IL-22和IL-10显著升高。综上所述，这些数据支持Tff蛋白在人类蠕虫感染中的作用。全球有数十亿人感染了寄生虫，特别是在资源匮乏的地区。这些感染可导致严重的发育迟缓、残疾和死亡。在容易获得的样本(如血清或尿液)中识别与感染状态相关的宿主生物标记物，将有利于对蠕虫感染的适当管理。我们的目标是确定参与组织修复和免疫调节的特定蛋白质是否会因感染巴西的特定蠕虫物种(钩虫和血吸虫的曼氏葡萄球菌)或尼日利亚的血吸虫血吸虫的血吸虫物种而改变。其中三叶因子2(TFF2)在巴西钩虫感染妇女血清中升高，而TFF3在女性高于男性，但也因曼氏吸虫血吸虫感染而增加。相比之下，感染嗜血杆菌的尼日利亚儿童血清中的两种转铁蛋白减少，而尿液中许多促炎细胞因子增加，卵子从宿主组织中冒出来。
Helminth infections, including hookworms and Schistosomes, can cause severe disability and death. Infection management and control would benefit from identification of biomarkers for early detection and prognosis. While animal models suggest that Trefoil Factor Family proteins (TFF2 and TFF3) and interleukin-33 (IL-33) -driven type 2 immune responses are critical mediators of tissue repair and worm clearance in the context of hookworm infection, very little is known about how they are modulated in the context of human helminth infection. We measured TFF2, TFF3, and IL-33 levels in serum from patients in Brazil infected with Hookworm and/or Schistosomes, and compared them to endemic and non-endemic controls. TFF2 was specifically elevated by Hookworm infection in females, not Schistosoma or co-infection. This elevation was correlated with age, but not worm burden. TFF3 was elevated by Schistosoma infection and found to be generally higher in females. IL-33 was not significantly altered by infection. To determine if this might apply more broadly to other species or regions, we measured TFFs and cytokine levels (IFNγ, TNFα, IL-33, IL-13, IL-1β, IL-17A, IL-22, and IL-10) in both the serum and urine of Nigerian school children infected with S. haematobium. We found that serum levels of TFF2 and 3 were reduced by infection, likely in an age dependent manner. In the serum, only IL-10 and IL-13 were significantly increased, while in urine IFN-γ, TNF-α, IL-13, IL-1β, IL-22, and IL-10 were significantly increased in by infection. Taken together, these data support a role for TFF proteins in human helminth infection. Billions of people are infected with parasitic helminths across the globe, especially in resource poor regions. These infections can result in severe developmental delay, disability, and death. Adequate management of helminth infection would benefit from the identification of host biomarkers in easily obtained samples (e.g. serum or urine) that correlate to infection state. Our goal was to determine if specific proteins involved in tissue repair and immune modulation are altered by infection with specific helminth species in Brazil (hookworm and S. mansoni species of blood fluke) or Nigeria (S. haematobium species of blood fluke). One of these proteins, Trefoil Factor 2 (TFF2), was elevated in the serum of hookworm infected women from Brazil, while another, TFF3 is higher in women than men, but also increased by S. mansoni blood fluke infection. In contrast, both TFFs were decreased in the serum of Nigerian children infected by S. haematobium, while many pro-inflammatory cytokines were increased in the urine, where the eggs emerge from host tissue.
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影响因子：
6.7
作者：
Fu CL;Odegaard JI;Herbert DR;Hsieh MH
通讯作者：
Hsieh MH
DOI：
10.1038/s41577-020-0301-x
发表时间：
2020-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.5
作者：
Karki R;Sharma BR;Tuladhar S;Williams EP;Zalduondo L;Samir P;Zheng M;Sundaram B;Banoth B;Malireddi RKS;Schreiner P;Neale G;Vogel P;Webby R;Jonsson CB;Kanneganti TD
通讯作者：
Kanneganti TD
影响因子：
3.5
作者：
Aribodor, Dennis N.;Bassey, Simon A.;Ugwuanyi, Ifeoma K.
通讯作者：
Ugwuanyi, Ifeoma K.
影响因子：
6
作者：
Hung, Li-Yin;Oniskey, Taylor K.;Herbert, De'Broski R.
通讯作者：
Herbert, De'Broski R.