Premium
Salmonella AvrA Modulates Innate Immune Signaling: A Mechanistic Analysis in Drosophila
Author(s) -
Jones Rheinallt,
Wentworth Christy,
Neish Andrew
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a132-d
Subject(s) - innate immune system , phosphorylation , biology , microbiology and biotechnology , effector , immune system , transfection , signal transduction , salmonella , nf κb , immunity , cell culture , bacteria , genetics
Many bacterial pathogens can influence eukaryotic immune signaling pathways by translocating preformed effector proteins into host cells. The Salmonella protein AvrA is known to have immunosuppressive effects in mammalian cells. We have studied the effects of AvrA in Drosophila, a model system with striking conservation between its immune signaling pathways and those of mammals. We created transgenic Drosophila harboring avrA under the transcriptional control of the yeast UAS promoter, allowing regulated expression of AvrA. Flies expressing AvrA were immuno‐compromised and failed to mount an anti‐microbial response specifically against gram negative bacteria. Drosophila expressing a catalytically inactive form of AvrA had a normal immune response. Further studies showed AvrA inhibited translocation of the NF‐kB homolog Relish, and unexpectedly, potently inhibited phosphorylation of the fly homologue of JNK. Studies in human cell culture recapitulated specific AvrA mediated inhibition of inducible JNK phosphorylation and NF‐kB inhibition. Furthermore, in cell culture transfected AvrA co‐immunoprecipitated with endogenous JNK showing that AvrA has direct interaction with JNK. These studies reveal Salmonella has evolved a protein able to inhibit the pro‐apoptotic JNK pathway while suppressing innate immunity. Research funding provided by the CCFA and Burroughs Welcome fund.