How Bacteria Bypass the Brain’s Defenses

To what extent is the integrity of our brain protected by barriers, and to what extent are these hermetic? The best known of these cerebral safeguards is the “blood-brain barrier”: this network of blood vessels, equipped with reinforced walls, runs through the brain and largely acts as a barrier to intruders (microbial agents, toxins, etc.). Despite everything, it is not inviolable: in the event of injury or disease, certain pathogens or metastatic cells, for example, manage to slip through its faults and invade the brain.

But it is the vulnerability of another rampart of the brain, the meninges, that an American team has just highlighted. Their study, published in the journal Nature the 1^is mars, reveals how certain bacteria manage to hijack the communication between the nerve fibers and the immune cells of the meninges, the membranes that envelop the brain and the spinal cord. A trick that allows them to neutralize the immune defenses of their host and to proliferate, causing dreadful meningitis.

According to the US Centers for Disease Control and Prevention (CDC), more than 1.2 million cases of bacterial meningitis are reported each year worldwide. In France, “After more than two years of low incidence, in connection with the measures put in place during the Covid-19 pandemic, the number of cases of invasive meningococcal infections has been on the rise since October 2022”, reported Public Health France, at the end of 2022. Untreated, these bacterial meningitis kill seven out of ten infected people. And, among the survivors, one in five retains serious sequelae: loss of hearing or vision, epileptic seizures, chronic headaches…

The key role of “macrophages”

“Until recently, the meninges seemed to be inert tissues without much interest. But, a few years ago, several teams including ours discovered that they harbor an incredible reserve of immune cells., notes Réjane Rua, from the Marseille-Luminy immunology center. Including certain cells called “macrophages”, which play a key role here.

A team from the Harvard Medical School has detailed, in mice, the cascade of steps that allows two pathogenic bacteria to break through the meningeal layers to infect the brain: Streptococcus pneumoniae et Streptococcus agalactiae, the main causes of bacterial meningitis in humans. The researchers focused on the outermost of the meninges, the dura mater, which houses not only a rich arsenal of immune cells, but also pain neurons, responsible for detecting mechanical pressure or the presence of toxins in particular.

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