生物谷報道：最新研究表明細(xì)菌會產(chǎn)生大量的人類蛋白復(fù)本擾亂早期免疫預(yù)警系統(tǒng),。根據(jù)這一現(xiàn)象可以改進(jìn)由細(xì)菌感染引起的疾病的治療方法,，如關(guān)節(jié)炎是由變態(tài)免疫反應(yīng)引起的。
巨噬和樹突狀細(xì)胞攜帶Toll-like受體可以通過監(jiān)測由細(xì)菌細(xì)胞膜和暴露物質(zhì)而引起免疫反應(yīng),。Toll-like受體可以將信號傳遞至另一種叫做MyD88的蛋白,，然后將其傳給其他分子，引起一系列免疫反應(yīng),。
細(xì)菌可以通過各種途徑逃避免疫監(jiān)測,。兩年前研究發(fā)現(xiàn)沙門氏菌可以合成一種蛋白質(zhì)使TIR失效,，但科學(xué)家不知道其中原因。
德國免疫學(xué)家Thomas Miethke和同事檢測了細(xì)菌基因組,，找出TIR相關(guān)蛋白的編碼序列,。這個小組本周在《自然.醫(yī)學(xué)》上發(fā)表文章稱已確定這種基因，其中包括模式生物大腸桿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,?？梢援a(chǎn)生與TIR相似的蛋白質(zhì)的大腸桿菌比沒有此編碼功能的大腸桿菌引起小鼠更嚴(yán)重的腎臟損傷。 因此,，引起較嚴(yán)重尿路感染的大腸桿菌大多可以編碼模仿人類TIR的蛋白質(zhì),。
研究者稱仿冒的TIR蛋白就像是一個圈套，它附著在MyD88蛋白上,，阻止其與TIR結(jié)合,，但是卻不激活其他免疫細(xì)胞。一種藥品可以抑制細(xì)菌的這種能力,，有望用于細(xì)菌感染的治療,。
生物谷推薦原始出處：
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: [email protected]
