How Bacteria Invade the Brain

Research shows bacteria hijack crosstalk between nerve and immune cells to cause meningitis

illustration of a nerve cell, a macrophage, and bacteria
Video: Rick Groleau

A new study led by researchers at Harvard Medical School details the step-by-step cascade that allows bacteria to break through the brain’s protective layers — the meninges — and cause brain infection, or meningitis, a highly fatal disease.

The research, conducted in mice and published March 1 in Nature, shows that bacteria exploit nerve cells in the meninges to suppress the immune response and allow the infection to spread into the brain.

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“We’ve identified a neuroimmune axis at the protective borders of the brain that is hijacked by bacteria to cause infection — a clever maneuver that ensures bacterial survival and leads to widespread disease,” said study senior author Isaac Chiu, associate professor of immunology in the Blavatnik Institute at HMS.

The study identifies two central players in this molecular chain of events that leads to infection — a chemical released by nerve cells and an immune cell receptor blocked by the chemical. The study experiments show that blocking either one can interrupt the cascade and thwart the bacterial invasion.

If replicated through further research, the new findings could lead to much-needed therapies for this hard-to-treat condition that often leaves those who survive with serious neurologic damage.

Such treatments would target the critical early steps of infection before bacteria can spread deep into the brain.

“The meninges are the final tissue barrier before pathogens enter the brain, so we have to focus our treatment efforts on what happens at this border tissue,” said study first author Felipe Pinho-Ribeiro, a former postdoctoral researcher in the Chiu lab, now an assistant professor at Washington University in St. Louis.

A recalcitrant disease in need of new treatments

More than 1.2 million cases of bacterial meningitis occur globally each year, according to the U.S. Centers for Disease Control and Prevention. Untreated, it kills seven out of 10 people who contract it. Treatment can reduce mortality to three in 10. However, among those who survive, one in five experience serious consequences, including hearing or vision loss, seizures, chronic headache, and other neurological problems.