Duke medical team finds genetic link between immune and nerve systems

[Guest guest]

Duke medical team finds genetic link between immune and nerve systems

http://www.eurekalert.org/pub_releases/2008-09/dumc-dmt091908.php

Duke University Medical Center researchers have discovered genetic

links between the nervous system and the immune system in a well-

studied worm, and the findings could illuminate new approaches to

human therapies.

For some time, researchers have theorized a direct link between the

nervous and immune systems, such as stress messages that override the

protective effects of antibodies, but the exact connection was

unknown.

" This is the first time that a genetic approach has been used to

demonstrate that specific neurons in the nervous system are capable

of regulating immune response in distant cells, " said

Aballay Ph.D., Assistant Professor in the Duke Department of

Molecular Genetics and Microbiology.

They studied a neural circuit in the roundworm Caenorhabditis elegans.

" The study of neural-immune communications is quite challenging in

mammals, " Aballay said. " The simple, well-characterized nervous

system of C. elegans and its recently discovered innate immune system

make it a prime system for research. We can study the mechanisms and

biological meaning of the cross-talk between the immune and nervous

systems, and our studies should set the stage for a new field of

research. "

Pamela Marino, Ph.D., who oversees molecular immunology grants at the

National Institute of General Medical Sciences of the National

Institutes of Health, said, " Dr. Aballay has made use of the well

defined genetics of the roundworm to reveal evidence of cross talk

between the nervous system and the innate immune system. Beyond

neuronal regulation of immunity, this work opens the door to

understanding how neurons may affect other non-neural processes, such

as fat storage and longevity. "

The study, published in the Sept. 18 issue of Science, was funded by

grants from the Whitehead Scholars Program and the National

Institutes of Health.

The research team used two approaches to show the genetic connection

between nerve cells and immune-response cells.

They found that NPR-1, a worm cell receptor linked to proteins that

are similar to mammalian neuropeptide Y, functions to suppress the

activity of specific neurons that block immune responses. They then

studied worms with a mutated npr-1 gene that produced an NPR-1

receptor that didn't function. The scientists showed that when the

flawed receptor didn't work, the neurons were able to block the

immune response and the worms became more susceptible to infection by

pathogens.

The three different neurons found to express the receptor NPR-1 are

exposed to the body fluids of the roundworm – the equivalent of the

bloodstream in humans. Signals from the neurons can travel and

communicate with other tissues, such as intestinal tissue, which

often directly contacts microbial pathogens, Aballay said.

They also performed a full-genome analysis on roundworms that had

altered nerve-cell function because of a mutation in the npr-1 gene.

This analysis showed the animals had poorly regulated expression of

genes that encode markers of innate immune responses. In particular,

they found that most of the immune marker genes were regulated by a

P38 MAPK signaling pathway, which is required for immunity in animals

from worms to humans.

" The complexity of the network involved in the communication between

the neural system and the immune system expands the number of

possible targets for therapeutic interventions, " Aballay said. " The

nervous system alone provides a large number of targets for novel

approaches to boost innate immunity against different pathogens. "