Pathogen-derived effectors trigger protective immunity via activation of the Rac2 enzyme and the IMD or Rip kinase signaling pathway.
Although infections with virulent pathogens often induce a strong inflammatory reaction, what drives the increased immune response to pathogens compared to nonpathogenic microbes is poorly understood. One possibility is that the immune system senses the level of threat from a microorganism and augments the response accordingly. Here, focusing on cytotoxic necrotizing factor 1 (CNF1), an Escherichia coli-derived effector molecule, we showed the host indirectly sensed the pathogen by monitoring for the effector that modified RhoGTPases. CNF1 modified Rac2, which then interacted with the innate immune adaptors IMD and Rip1-Rip2 in flies and mammalian cells, respectively, to drive an immune response. This response was protective and increased the ability of the host to restrict pathogen growth, thus defining a mechanism of effector-triggered immunity that contributes to how metazoans defend against microbes with pathogenic potential.
Developmental Immunology, Massachusetts General Hospital/Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. boyerl@unice.fr
Laurent
L
Boyer
Lorin
L
Magoc
Stephanie
S
Dejardin
Michael
M
Cappillino
Nicholas
N
Paquette
Charlotte
C
Hinault
Guillaume M
GM
Charriere
W K Eddie
WK
Ip
Shannon
S
Fracchia
Elizabeth
E
Hennessy
Deniz
D
Erturk-Hasdemir
Jean-Marc
JM
Reichhart
Neal
N
Silverman
Adam
A
Lacy-Hulbert
Lynda M
LM
Stuart
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D004789:Enzyme Activation; D057809:HEK293 Cells; D006801:Humans; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D020744:rac GTP-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D000097766:RAC2 GTP-Binding Protein
D048868:Adaptor Proteins, Signal Transducing; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D020744:rac GTP-Binding Proteins; D000097766:RAC2 GTP-Binding Protein