Circulating microbial products and acute phase proteins as markers of pathogenesis in lymphatic filarial disease.
Circulating microbial products and acute phase proteins as markers of pathogenesis in lymphatic filarial disease.
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DOI：
10.1371/journal.ppat.1002749
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发表时间：
2012
期刊：
影响因子：
6.7
通讯作者：
Babu S
中科院分区：
文献类型：
--
作者：
Anuradha R;George PJ;Pavan Kumar N;Fay MP;Kumaraswami V;Nutman TB;Babu S
淋巴丝虫病可以与严重的病理发展有关，在一部分感染患者中表现为水肿、鞘膜积液和象皮肿。宿主炎症反应失调导致全身免疫激活被认为在丝虫病发病机制中起核心作用。我们测量了慢性丝虫病伴（CP Ag+）或不伴（CP Ag−）活动性感染、临床无症状感染（INF）和无感染（地方病正常[EN]）个体的微生物易位标记物、急性期蛋白和炎性细胞因子的血浆水平。两个活动性感染组（CP Ag+与INF相比）和无活动性感染组（CP Ag-与EN相比）之间的比较初步用于确定发病机制的标志物。此后，我们使用标记物的对数转换响应的线性模型测试了所有四个组中的组效应。我们的数据表明，循环中微生物易位产物（脂多糖和LPS结合蛋白）、急性时相蛋白（结合珠蛋白和血清淀粉样蛋白-A）和炎性细胞因子（IL-1β、IL-12和TNF-α）的水平与淋巴丝虫感染疾病的发病机制相关，并暗示循环微生物产物和急性时相蛋白的重要作用。淋巴丝虫病困扰着全世界超过1.2亿人。虽然这种感染大多数在临床上没有症状，但约有4 000万人患有明显的病态临床病理学，其特征是阴囊区和下肢肿胀（鞘膜积液和水肿）。影响这些个体疾病发病机制的宿主免疫因素尚未完全了解。循环微生物产物如LPS和与微生物易位相关的标志物已被证明在某些感染如HIV的疾病发病机制中起重要作用。同样，与急性期反应相关的蛋白质和相关细胞因子也在发病机制中发挥重要作用。我们试图通过比较四组个体中各种标志物的血浆水平来阐明上述因素在疾病发病机制中的作用：有或没有活动性丝虫感染的慢性病理个体，无症状的丝虫感染个体和未感染的地方性正常个体。我们发现，循环水平的脂多糖，急性期蛋白和某些细胞因子显着升高，在丝虫病与活动性感染，但不是在其他组表明，丝虫感染诱导这些因素的生产增加与丝虫淋巴病理的发展。
Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathogenesis. We measured the plasma levels of microbial translocation markers, acute phase proteins, and inflammatory cytokines in individuals with chronic filarial pathology with (CP Ag+) or without (CP Ag−) active infection; with clinically asymptomatic infections (INF); and in those without infection (endemic normal [EN]). Comparisons between the two actively infected groups (CP Ag+ compared to INF) and those without active infection (CP Ag− compared to EN) were used preliminarily to identify markers of pathogenesis. Thereafter, we tested for group effects among all the four groups using linear models on the log transformed responses of the markers. Our data suggest that circulating levels of microbial translocation products (lipopolysaccharide and LPS-binding protein), acute phase proteins (haptoglobin and serum amyloid protein-A), and inflammatory cytokines (IL-1β, IL-12, and TNF-α) are associated with pathogenesis of disease in lymphatic filarial infection and implicate an important role for circulating microbial products and acute phase proteins. Lymphatic filariasis afflicts over 120 million people worldwide. While the infection is mostly clinically asymptomatic, approximately 40 million people suffer from overt, morbid clinical pathology, characterized by swelling of the scrotal area and lower limbs (hydrocele and lymphedema). Host immunologic factors that influence the pathogenesis of disease in these individuals are not completely understood. Circulating microbial products such as LPS and markers associated with microbial translocation have been shown to play an important role in disease pathogenesis of certain infections like HIV. Similarly, proteins associated with the acute phase response and related cytokines also play an important role in pathogenesis. We have attempted to elucidate the role of the above mentioned factors in disease pathogenesis by comparing the plasma levels of the various markers in four groups of individuals: chronic pathology individuals with or without active filarial infection, asymptomatic, filarial infected individuals and uninfected, endemic normal individuals. We show that circulating levels of LPS, acute phase proteins and certain cytokines are significantly elevated in filarial disease with active infection but not in the other groups indicating that filarial infection induced increased production of these factors correlated with the development of filarial lymphatic pathology.
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影响因子：
56.9
作者：
COHEN, IR;NORINS, LC
通讯作者：
NORINS, LC
影响因子：
2
作者：
Levels, Johannes H. M.;Geurts, Pierre;Meijers, Joost C. M.
通讯作者：
Meijers, Joost C. M.
影响因子：
4.1
作者：
Nixon DE;Landay AL
通讯作者：
Landay AL
影响因子：
9.1
作者：
LAL, RB;DHAWAN, RR;GAD, AA
通讯作者：
GAD, AA
影响因子：
2.2
作者：
Nutman, TB;Kumaraswami, V
通讯作者：
Kumaraswami, V