When you let your guard down, external forces find a way for an unwarranted invasion. Many bacteria use this strategy to cause an infection in the human body.
And the brain is no exception, as is seen in the case of bacterial meningitis.
Scientists from Harvard Medical School, USA, investigated how bacteria infiltrate the brain to cause the infection. The study on mice, published in Nature on 1 March, maps a step-by-step process on how the bacteria gain entry by deactivating the immune warriors that are present on the meninges – the brain’s covering.
The invasion
Bacterial meningitis is a life-threatening infection of the meninges and the central nervous system, affecting more than 2.5 million people a year. Streptococcus pneumoniae and Streptococcus agalactiae are the primary culprits behind these infections.
“Many people who recover from meningitis develop neurological damage and long-term effects on the brain including chronic headache and cognitive decline,” Isaac Chiu, senior author of the study and associate professor of immunology at the Blavatnik Institute, Harvard Medical School, USA, tells Happiest Health.
Peeling the layers
The major sentries of the brain are the meninges which comprise three layers: an outer fibrous dura mater, a middle weblike arachnoid mater, and an inner delicate pia mater.
In their experiments in mice, the researchers observed that the invading bacteria released certain toxic chemicals which formed pores in the outer dura mater. These pores compromised the stability of the layers. The team also noticed the toxins latched on to the dura mater’s pain neurons.
An earlier study shows that the brain perceives pain such as a headache in the outer layers via these neurons and not inside the brain.
“We have found that pain nerve fibres signal directly to immune cells in the meninges to change their function,” says Dr Chiu.
Dr Chiu further explains that these pain neurons produce an inflammatory protein called CGRP (calcitonin gene-related peptide). This protein binds itself to a receptor on the immune cells of the dura mater. This binding prevents the immune cells from performing their protective functions, thus breaking the defences from within. A weakened immune response enables the bacteria to cause the infection.
The scientists identified this route of infection as a neuroimmune axis.
Read more: Secret allies: the brain and the immune system
Decoding the route
The scientists dived deeper into the neuroimmune pathway to understand and see if it offered scope for effective treatment strategies. Dr Chiu and his team focused on the dura mater as it has more blood vessels. “This is likely one reason the bacteria can invade the dura so easily, and we think bacteria reach it mainly through these meningeal blood vessels,” he says.
When the team looked at the dura mater’s blood vessels closely under an advanced microscope, they found that the pain neurons and immune cells lie close to each other.
When they blocked the pain neurons in one group of mice, the bacterial load was lesser, and the immune cells were more in number. They saw similar results when they blocked the activity of CGRP with a chemical. They even blocked the immune receptor and saw that the mice had no infection. With these inputs, they concluded that using chemicals to block CGRP and immune receptor activity could be a possible mode of treatment for bacterial meningitis.
Possible treatment steps
While treatment options such as antibiotics and steroids are available for the infection, they are not potent enough and only tame it. In addition, they cannot prevent post-infection complications. The steroids usually reduce inflammation, but they further suppress the immune system, which could worsen the infection. Moreover, there are no effective vaccines against bacterial meningitis.
Dr Chiu hopes that the current study will offer some possibilities for treatment. “Given how high the mortality rate is and the post-infectious consequences of meningitis, it would be exciting to know if targeting the neuroimmune axis can enhance the treatment of meningitis,” he says.
His team also aims to understand how different pathogens in the meninges may activate the pain fibres.
