Tauszig-Delamasure Servane, Bilak Hana, Capovilla Maria, Hoffmann Jules A, Imler Jean-Luc
UPR9022 du Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, 15, rue René Descartes, 67000 Strasbourg, France.
Nat Immunol. 2002 Jan;3(1):91-7. doi: 10.1038/ni747. Epub 2001 Dec 17.
We report here the identification and functional characterization of DmMyD88, a gene encoding the Drosophila homolog of mammalian MyD88. DmMyD88 combines a Toll-IL-1R homology (TIR) domain and a death domain. Overexpression of DmMyD88 was sufficient to induce expression of the antifungal peptide Drosomycin, and induction of Drosomycin was markedly reduced in DmMyD88-mutant flies. DmMyD88 interacted with Toll through its TIR domain and required the death domain proteins Tube and Pelle to activate expression of Drs, which encodes Drosomycin. DmMyD88-mutant flies were highly susceptible to infection by fungi and Gram-positive bacteria, but resisted Gram-negative bacterial infection much as did wild-type flies. Phenotypic comparison of DmMyD88-mutant flies and MyD88-deficient mice showed essential differences in the control of Gram-negative infection in insects and mammals.
我们在此报告DmMyD88的鉴定及功能特性，该基因编码哺乳动物MyD88的果蝇同源物。DmMyD88结合了一个Toll-IL-1R同源（TIR）结构域和一个死亡结构域。DmMyD88的过表达足以诱导抗真菌肽果蝇抗菌肽的表达，而在DmMyD88突变果蝇中，果蝇抗菌肽的诱导表达显著降低。DmMyD88通过其TIR结构域与Toll相互作用，并需要死亡结构域蛋白Tube和Pelle来激活编码果蝇抗菌肽的Drs的表达。DmMyD88突变果蝇对真菌和革兰氏阳性菌感染高度敏感，但对革兰氏阴性菌感染的抵抗力与野生型果蝇相当。DmMyD88突变果蝇与MyD88缺陷小鼠的表型比较显示，昆虫和哺乳动物在革兰氏阴性菌感染控制方面存在本质差异。
