The Drosophila melanogaster toll pathway participates in resistance to infection by the gram-negative human pathogen Pseudomonas aeruginosa

被引:126
作者
Lau, GW
Goumnerov, BC
Walendziewicz, CL
Hewitson, J
Xiao, WZ
Mahajan-Miklos, S
Tompkins, RG
Perkins, LA
Rahme, LG
机构
[1] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA
[3] Shriners Burns Inst, Boston, MA 02114 USA
[4] Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA
[5] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA
关键词
D O I
10.1128/IAI.71.7.4059-4066.2003
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Pseudomonas aeruginosa is a gram-negative pathogen that infects immunocompromised and cystic fibrosis patients. The molecular basis of the host-P. aeruginosa interaction and the effect of specific P. aeruginosa virulence factors on various components of the innate immunity pathways are largely unknown. We examine interactions between P. aeruginosa virulence factors and components of innate immunity response in the Drosophila melanogaster model system to reveal the importance of the Toll signaling pathway in resistance to infection by the P. aeruginosa human isolate PA14. Using the two PA14-isogenic mutants plcS and dsbA, we show that Drosophila loss-of-function mutants of Spatzle, the extracellular ligand of Toll, and Dorsal and Dif, two NF-kappaB-like transcription factors, allow increased P. aeruginosa infectivity within fly tissues. In contrast, a constitutively active Toll mutant and a loss-of-function mutant of Cactus, an IkappaB-like factor that inhibits the Toll signaling, reduce infectivity. Our finding that Dorsal activity is required to restrict P. aeruginosa infectivity in Drosophila provides direct in vivo evidence for Dorsal function in adult fly immunity. Additionally, our results provide the basis for future studies into interactions between P. aeruginosa virulence factors and components of the Toll signaling pathway, which is functionally conserved between flies and humans.
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页码:4059 / 4066
页数:8
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