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Figure: Parasites and macrophages in the meninges
Source: (c) Kiavash Movahedi
The team led by Professor Kiavash Movahedi (VUB, VIB) has mapped in detail how the immune system fights pathogens that invade the brain
.
These findings shed light on host-pathogen interactions and the long-term consequences of
brain infections.
The findings, published in the prestigious journal Immunity, show how different types of immune cells are involved in fighting infections in the
brain.
The researchers were able to demonstrate that the first line of defense is formed by macrophages that inhabit the brain, a type of white blood cell
that already lives in a healthy brain.
These macrophages then recruit large numbers of blood-derived macrophages to help control the disease
.
Once the infection is resolved, these "recruited macrophages" quickly disappear
again.
The brain and its defense against infectionMovahedi: "This study shows the extraordinary ability
of the brain's immune system to quickly return to its normal state.
But we can also observe how certain cells remain changed long after healing, possessing a kind of "memory"
of infection.
This suggests that during a person's lifetime, when we may suffer multiple infections – think of the Covid-19 pandemic, for example – the function of tissue macrophages may change
.
Does this early brain infection affect the likelihood of developing other neurological disorders, such as multiple sclerosis or dementia? This will undoubtedly become a hot topic
in the future research community.
”
The brain is like a central command post, controlling every process
in our body.
Therefore, the brain must also be able to protect itself from the effects of
disease.
This is achieved in part by limiting the complex barriers that enter the
brain.
Immune cells form another line
of defense.
Despite these different layers of defense, some pathogens still manage to penetrate, which can lead to life-threatening diseases
.
However, even if the infection is eventually successfully controlled and the pathogen is eliminated, patients may suffer from neurological problems for years to come
.
Therefore, it is important to
better understand the dynamics of host-pathogen interactions and their long-term consequences.
Professor Movahedi's team investigated the infection with the trypanosoma genus brucei, a dangerous microorganism
that invades the brain.
These single-celled parasites live in sub-Saharan Africa and can cause deadly neuropathology
.
Although these parasites have long been known to invade the brain, the nature of infection pathways and host responses remains poorly
understood.
The team studied the infection in mice, which, like humans, are very sensitive
to the disease.
They found that the parasite first invades the limbic tissues of the brain, namely the meninges and choroidal plexus, and then into fluid-filled cavities and neuronal tissue
.
Using some advanced techniques, the researchers also mapped the immune system's response
in detail.
Macrophages, in particular, play an important role
.
They occupy the first line of defense and send signals to the rest of the body to attract immune cells from the blood into the brain
.
Most of these "newly recruited" immune cells are also macrophages, but they behave differently than
their resident cells.
"Our findings place macrophages at the center of pathogen invasion in the brain and show how local and recruited macrophages play different roles
during infection.
For example, immune cells in the blood exhibit higher expression of
antimicrobial proteins.
This shows that they are able to destroy the parasite very well," said
Karen de Flamink, a doctoral student and first author of the study.
The team then investigated what happened to
all these immune cells after the disease was successfully treated.
Memory of the brainProfessor Movahedi said: "We were surprised that when the parasites were
eliminated, the macrophages absorbed in the blood quickly disappeared from the brain.
This underscores how important it
is for the brain to quickly return to its normal state once the infection has been treated.
”
The team found that resident macrophages in limbic areas of the brain remained more active for months after the parasite was cleared, suggesting that they retained some sort of "memory"
about the infection.
Studies of other tissues have shown that this infection-induced memory can alter macrophages' ability to
respond to future insults.
Article Differential plasticity and fate of brain-resident and recruited macrophages during the onset and resolution of neuroinflammation"However, it's not as scary as it sounds," de Flamink said
.
"As we begin to understand the long-term effects of infection on the brain, research can begin to focus on finding new therapies to address and reverse dysfunction caused by underlying infection
.
"
