Responses of murine and human macrophages to leptospiral infection: a study using comparative array analysis.
Responses of murine and human macrophages to leptospiral infection: a study using comparative array analysis.
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小鼠和人类巨噬细胞对钩端螺旋体感染的反应：使用比较阵列分析的研究。
DOI：
10.1371/journal.pntd.0002477
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发表时间：
2013
影响因子：
3.8
通讯作者：
Gu J
中科院分区：
文献类型：
--
作者：
Xue F;Zhao X;Yang Y;Zhao J;Yang Y;Cao Y;Hong C;Liu Y;Sun L;Huang M;Gu J
钩端螺旋体病是由致病性钩端螺旋体引起的一种再次出现的热带传染病。不同的宿主先天免疫反应与钩端螺旋体病的严重程度不同有关。在这项研究中，我们使用转录组学和细胞因子阵列来比较计算小鼠腹膜巨噬细胞(MPM)和人外周血单核细胞(HBMS)对钩端螺旋体感染的反应。我们发现了这两种免疫细胞的一系列不同的表达谱。MPM在抗原处理和提呈、膜电位调节、天然免疫反应等几个生物学过程中的调控基因所占比例远高于HBMS(>；2倍)。在MPMS和HBMS中，caspase-8和具有死亡结构域的Fas相关蛋白(FADD)样的凋亡调节基因显著上调，这支持了先前的结果，即caspase-8和caspase-3通路在钩端螺旋体感染的巨噬细胞凋亡中起重要作用。此外，补体途径的关键成分C3只在MPM中上调。此外，几种细胞因子，如白介素10(IL-10)和肿瘤坏死因子-α(TNF-α)，在MPM和HBMS的mRNA和蛋白水平上都有差异表达。其中一些差异表达被证明是致病钩端螺旋体在mRNA或蛋白质水平上的特异性调控。虽然目前尚不清楚为什么有些动物对钩端螺旋体具有抵抗力，而另一些动物对钩端螺旋体感染易感，但这项基于转录和细胞因子阵列的比较研究部分揭示了小鼠对钩端螺旋体病的抵抗力和人类对钩端螺旋体病的易感性的差异。综上所述，这些发现将有助于进一步研究钩端螺旋体感染的先天性免疫反应。
Leptospirosis is a re-emerging tropical infectious disease caused by pathogenic Leptospira spp. The different host innate immune responses are partially related to the different severities of leptospirosis. In this study, we employed transcriptomics and cytokine arrays to comparatively calculate the responses of murine peritoneal macrophages (MPMs) and human peripheral blood monocytes (HBMs) to leptospiral infection. We uncovered a series of different expression profiles of these two immune cells. The percentages of regulated genes in several biological processes of MPMs, such as antigen processing and presentation, membrane potential regulation, and the innate immune response, etc., were much greater than those of HBMs (>2-fold). In MPMs and HBMs, the caspase-8 and Fas-associated protein with death domain (FADD)-like apoptosis regulator genes were significantly up-regulated, which supported previous results that the caspase-8 and caspase-3 pathways play an important role in macrophage apoptosis during leptospiral infection. In addition, the key component of the complement pathway, C3, was only up-regulated in MPMs. Furthermore, several cytokines, e.g. interleukin 10 (IL-10) and tumor necrosis factor alpha (TNF-alpha), were differentially expressed at both mRNA and protein levels in MPMs and HBMs. Some of the differential expressions were proved to be pathogenic Leptospira-specific regulations at mRNA level or protein level. Though it is still unclear why some animals are resistant and others are susceptible to leptospiral infection, this comparative study based on transcriptomics and cytokine arrays partially uncovered the differences of murine resistance and human susceptibility to leptospirosis. Taken together, these findings will facilitate further molecular studies on the innate immune response to leptospiral infection.
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DOI：
10.1128/cdli.10.2.332-335.2003
发表时间：
2003-03-01
期刊：
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子：
--
作者：
de Fost, M;Hartskeerl, RA;van der Poll, T
通讯作者：
van der Poll, T
影响因子：
3.1
作者：
Brown, JP;Zachary, JF;Wooten, RM
通讯作者：
Wooten, RM
影响因子：
3.1
作者：
Hauk, Pricila;Macedo, Felipe;Ho, Paulo Lee
通讯作者：
Ho, Paulo Lee
影响因子：
3.1
作者：
Hoke, David E.;Egan, Suhelen;Adler, Ben
通讯作者：
Adler, Ben
影响因子：
2.1
作者：
Cinco, M;Vecile, E;Dobrina, A
通讯作者：
Dobrina, A