Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study shows role of disease-fighting cells in HIV-related neurological damage

12.05.2015

Findings add to evidence macrophage accumulation is central to brain injury

Despite symptom-stifling anti-retroviral drugs, as many as half of all patients living with HIV experience neurological damage tied to chronic inflammation in the brain fueled by the body's own immune defenses.


Dyes illuminate macrophage and monocyte cells as they arrive in the brain, where their presence is tied to neurological damage in people otherwise living symptom-free with HIV. By using different colored dyes to tag these disease-fighting cells, researchers have developed a clearer picture of how and when macrophages and monocytes accumulate in different parts of the brain during stages of HIV infection and the onset of AIDS. The findings, reported in the American Journal of Pathology, add new evidence about the role of these cells in AIDS-related dementia and other illnesses.

Credit: Amer. Journal of Pathology

In an effort to understand why patients who appear virus free are afflicted with AIDS-related dementia and other illnesses, researchers have focused on disease-fighting cells, called macrophages and monocytes, as they traffic throughout the body and into the brain.

But little has been known about the timing and dynamics behind these types of white blood cells as they invade the central nervous system during the initial stages of HIV infection or at the onset of AIDS.

A new investigative approach in SIV-infected rhesus monkeys has yielded fresh clues that show the caustic interplay between macrophage and monocyte traffic in the central nervous system and the onset of HIV infection and the formation of brain lesions tied to neurological damage, according to a new report in the online edition of the American Journal of Pathology.

Researchers from Boston College, the University of Florida and Tulane University Health Science Center report macrophages accumulate in different parts of the brain during different stages of initial infection, a finding that clarifies the spread of infection to the brain is a multi-layered and dynamic process.

"This type of approach allowed us to label macrophages in the perivascular space in the brain to identify macrophage and monocyte traffic to the brain in the early, mid and late stages of infection," said Boston College Professor of Biology Kenneth Williams, the senior author of the report. "We now know what cells bring the virus to the brain and what cells contribute to neurological damage in the brain, as well as the timing of the entry of these cells and when the pathologic virus enters. These are two big questions researchers have had."

The researchers tagged monocytes, destined to enter the brain, in bone marrow with a biochemical marker known as BrdU and also used a series of different color dyes to label macrophages as they entered the central nervous system at different times in infection, including early, mid and terminal states. As infection progressed, the researchers found MAC387 macrophages accumulated in the meninges and choroid plexus in early-stage brain infection. Later on, MAC387 macrophages were found in perivascular spaces that surround arteries and veins in the brain, as well as at sites where brain lesions would form.

Another macrophage, known as CD163 macrophages, was traced to perivascular space and brain lesions during the late stage, the team reports. Late in infection, the volume of macrophages entering the brain was nearly three times as great as during early-stage infection.

"An important question researchers have is what drives the pathology and the resulting damage in the brain?" said Williams. "Is it the virus itself or macrophage and monocyte cells? What we found is that these cells that arrive late with the development of AIDS have a 2.9-fold higher percentage of being infected with the virus. So there is a dramatic increase in the viral load as infection progresses that correlates to macrophage accumulation."

Turning their attention to lesion formation, the researchers discovered that greater than 80 percent of the macrophages found in the lesions were present in the brain prior to lesion formation. The surprising finding suggests the cells in the lesions migrated from non-lesion sites in the brain rather than from outside the brain.

"Brain lesions are central to understanding what causes AIDS-related dementia," said Williams. "In early stages of infection, we could see two or three macrophages scattered along the vessel. By the late stage, when lesions appeared, there were 30 to 50 at the site. What we found is that a majority of the cells in the lesions were present in the brain at an early stage. So these macrophages are migrating from the brain to the lesion sites, which shows a complex and dynamic level of activity."

Media Contact

Ed Hayward
ed.hayward@bc.edu
617-552-4826

 @BostonCollege

http://www.bc.edu 

Ed Hayward | EurekAlert!

Further reports about: HIV brain lesions central nervous system damage macrophage macrophages nervous neurological

More articles from Life Sciences:

nachricht Two Group A Streptococcus genes linked to 'flesh-eating' bacterial infections
25.09.2017 | University of Maryland

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Fraunhofer ISE Pushes World Record for Multicrystalline Silicon Solar Cells to 22.3 Percent

25.09.2017 | Power and Electrical Engineering

Usher syndrome: Gene therapy restores hearing and balance

25.09.2017 | Health and Medicine

An international team of physicists a coherent amplification effect in laser excited dielectrics

25.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>