[转移贴]Nature Medicine：细菌模仿人体蛋白引起免疫变态反应

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原贴由Rojjer发表于 2008-3-11 22:40
http://biosky.haotui.com/thread-4171-1-5.html

最新研究表明细菌会产生大量的人类蛋白复本扰乱早期免疫预警系统。根据这一现象可以改进由细菌感染引起的疾病的治疗方法，如关节炎是由变态免疫反应引起的。

巨噬和树突状细胞携带Toll-like受体可以通过监测由细菌细胞膜和暴露物质而引起免疫反应。Toll-like受体可以将信号传递至另一种叫做MyD88的蛋白，然后将其传给其他分子，引起一系列免疫反应。

细菌可以通过各种途径逃避免疫监测。两年前研究发现沙门氏菌可以合成一种蛋白质使TIR失效，但科学家不知道其中原因。

德国免疫学家Thomas Miethke和同事检测了细菌基因组，找出TIR相关蛋白的编码序列。这个小组本周在《自然.医学》上发表文章称已确定这种基因，其中包括模式生物大肠杆菌的一段可以引起尿路感染的序列和一段葡萄球菌抗氨卞的序列。可以产生与TIR相似的蛋白质的大肠杆菌比没有此编码功能的大肠杆菌引起小鼠更严重的肾脏损伤。 因此，引起较严重尿路感染的大肠杆菌大多可以编码模仿人类TIR的蛋白质。

研究者称仿冒的TIR蛋白就像是一个圈套，它附着在MyD88蛋白上，阻止其与TIR结合，但是却不激活其他免疫细胞。一种药品可以抑制细菌的这种能力，有望用于细菌感染的治疗。

Nature Medicine
Published online: 9 March 2008 | doi:10.1038/nm1734


Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain–containing proteins
Christine Cirl1, Andreas Wieser2, Manisha Yadav3, Susanne Duerr1, Sören Schubert2, Hans Fischer3, Dominik Stappert3, Nina Wantia1, Nuria Rodriguez1, Hermann Wagner1, Catharina Svanborg3 & Thomas Miethke1

Abstract
Pathogenic microbes have evolved sophisticated molecular strategies to subvert host defenses. Here we show that virulent bacteria interfere directly with Toll-like receptor (TLR) function by secreting inhibitory homologs of the Toll/interleukin-1 receptor (TIR) domain. Genes encoding TIR domain containing–proteins (Tcps) were identified in Escherichia coli CFT073 (TcpC) and Brucella melitensis (TcpB). We found that TcpC is common in the most virulent uropathogenic E. coli strains and promotes bacterial survival and kidney pathology in vivo. In silico analysis predicted significant tertiary structure homology to the TIR domain of human TLR1, and we show that the Tcps impede TLR signaling through the myeloid differentiation factor 88 (MyD88) adaptor protein, owing to direct binding of Tcps to MyD88. Tcps represent a new class of virulence factors that act by inhibiting TLR- and MyD88-specific signaling, thus suppressing innate immunity and increasing virulence.

Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, Trogerstrasse 30, D-81675 München, Germany.
Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universität, Pettenkoferstrasse 9a, D-80336 München, Germany.
Department of Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Sölvegatan 23, 22362 Lund, Sweden.
Correspondence to: Thomas Miethke1 e-mail: Thomas.Miethke@lrz.tum.de