New Insights into How Tuberculosis Bacteria Invades the Brain

Researchers at the Francis Crick Institute have uncovered the mechanisms by which Mycobacterium tuberculosis, the bacterium responsible for tuberculosis (TB), breaches the protective blood-brain barrier, leading to severe brain infections such as meningitis. Meningitis, a rare but critical complication affecting 1% to 10% of TB cases, poses significant treatment challenges. The study further explored the influence of HIV co-infection on TB bacteria's ability to infect brain cells.

In their experiments, scientists introduced TB bacteria to various brain cell types, including astrocytes, pericytes, microglia, and endothelial cells, observing that the bacteria could infect and proliferate within each cell type. Notably, prior infection with HIV increased bacterial entry into some cells, like astrocytes and pericytes, although it did not affect endothelial cells directly. After two days, the bacteria thrived across all cell types, with HIV co-infection enhancing growth in pericytes and endothelial cells. This suggests that HIV may facilitate TB infiltration via a bystander effect.

To simulate the blood-brain barrier, the team constructed a 3D model using pericytes and astrocytes on either side of a porous membrane, with microglia included to mimic the brain environment. Findings revealed that TB bacteria compromised the integrity of this barrier, increasing its permeability within days—independent of HIV co-infection. Cell layer damage was evident, with the bacteria causing a buildup of damaging molecules like glutamate, reactive oxygen species, and inflammatory compounds, and rendering astrocytes toxic to nerve cells.

The core conclusion is that TB bacteria can breach the brain’s defenses by directly damaging the blood-brain barrier, offering an alternative to the previously hypothesized mechanism involving immune cell hijacking. Although HIV seemed not to increase barrier leakiness, it might still promote bacterial entry and growth by weakening cellular defenses.

Experts emphasize the importance of these findings in developing treatments that prevent TB from entering the brain or drugs capable of crossing the compromised blood-brain barrier. As HIV co-infection exacerbates TB’s impact on the brain, understanding these interactions is vital for managing co-infected patients effectively.

This research sheds new light on TB neuropathogenesis and highlights the need for targeted strategies to protect the brain from TB invasion, especially in populations with high HIV prevalence.

Source: https://medicalxpress.com/news/2025-05-scientists-explore-tb-bacteria-brain.html