How meningitis-causing micro organism invade the mind

Micro organism can slip into the mind by commandeering cells within the mind’s protecting layers, a brand new examine finds. The outcomes trace at how a lethal an infection known as bacterial meningitis takes maintain.

In mice contaminated with meningitis-causing micro organism, the microbes exploit previously unknown communication between pain-sensing nerve cells and immune cells to slide by the mind’s defenses, researchers report March 1 in Nature. The outcomes additionally trace at a brand new strategy to probably delay the invasion — utilizing migraine medicines to interrupt these cell-to-cell conversations.

Bacterial meningitis is an an infection of the protecting layers, or meninges, of the mind that impacts 2.5 million individuals globally per yr. It might probably trigger extreme complications and generally lasting neurological harm or loss of life.

“Unexpectedly, ache fibers are literally hijacked by the micro organism as they’re attempting to invade the mind,” says Isaac Chiu, an immunologist at Harvard Medical Faculty in Boston. Usually, one would possibly count on ache to be a warning system for us to close down the micro organism in a roundabout way, he says. “We discovered the other…. This [pain] sign is being utilized by the micro organism for a bonus.”

It’s identified that pain-sensing neurons and immune cells coexist within the meninges, significantly within the outermost layer known as the dura mater (SN: 11/11/20). So to see what function the ache and immune cells play in bacterial meningitis, Chiu’s staff contaminated mice with two of the micro organism identified to trigger the an infection in people: Streptococcus pneumoniae and S. agalactiae. The researchers then noticed the place that micro organism ended up in mice genetically tweaked to lack pain-sensing nerve cells and in contrast these resting spots to these in mice with the nerve cells intact.

Mice with out pain-sensing neurons had fewer micro organism within the meninges and mind than these with the nerve cells, the staff discovered. This contradicts the concept ache in meningitis serves as a warning sign to the physique’s immune system, mobilizing it for motion.

Additional checks confirmed that the micro organism triggered a sequence of immune-suppressing occasions, beginning with the microbes secreting toxins within the dura mater.

The toxins hitched onto the ache neurons, which in flip launched a molecule known as CGRP. This molecule is already identified to bind to a receptor on immune cells, the place it helps management the dura mater’s immune responses. Injecting contaminated mice with extra CGRP lowered the variety of dural immune cells and helped the an infection alongside, the researchers discovered.

The staff additionally seemed extra carefully on the receptor that CGRP binds to. In contaminated mice bred with out the receptor, fewer micro organism made it into the mind. However in ones with the receptor, immune cells that may in any other case engulf micro organism and recruit reinforcements have been disabled.

The findings recommend that both stopping the discharge of CGRP or stopping it from binding to immune cells would possibly assist delay an infection.

In people, neuroscientists know that CGRP is a driver of complications — it’s already a goal of migraine medicines (SN: 6/5/18). So the researchers gave 5 mice the migraine treatment olcegepant, which blocks CGRP’s results, and contaminated them with S. pneumoniae. After an infection, the medicated mice had much less micro organism within the meninges and mind, took longer to point out signs, didn’t lose as a lot weight and survived longer than mice that weren’t given the treatment.

The discovering suggests olcegepant slowed the an infection. Although it solely purchased mice just a few additional hours, that’s essential in meningitis, which may develop simply as shortly. Had been olcegepant to work the identical means in people, it would give medical doctors extra time to deal with meningitis. However the impact might be not as dramatic in individuals, cautions Michael Wilson, a neurologist on the College of California, San Francisco who wasn’t concerned with the work.

Scientists nonetheless want to find out whether or not pain-sensing nerve cells and immune cells have the identical rapport in human dura mater, and whether or not migraine medication might assist deal with bacterial meningitis in individuals.

Neurologist Avindra Nath has doubts. Clinicians suppose the immune response and irritation injury the mind throughout meningitis, says Nath, who heads the staff investigating nervous system infections on the Nationwide Institute of Neurological Issues and Stroke in Bethesda, Md. So therapy entails medication that suppress the immune response, somewhat than improve it as migraine medicines would possibly. 

Chiu acknowledges this however notes there could be room for each approaches. If dural mater immune cells might head the an infection off on the cross, it could preserve some micro organism from penetrating the defenses, minimizing mind irritation.

This examine won’t finally change how clinicians deal with sufferers, Wilson says. However it nonetheless reveals one thing new about one of many first strains of protection for the mind.