HIV v immune system is the focus

Alasdair Leslie

Alasdair Leslie certainly doesn’t fit the prototype description of the studious and bespectacled boffin tucked behind a row of petri dishes.

A quirky modernist, with a sense of fun, he will be part of a clinical and diagnostic in-vestigative team taking up a research post at the new KwaZulu-Natal Research Institute for TB and HIV.

Career change, marriage and two young children stand between him and the last time he lived in Africa, but he makes no bones about the fact that he still has a passion for the stark and expansive landscapes that he fell in love with some years ago as a volunteer teacher.

“When I returned to the UK in 2002 with my now wife, Georgie, part of me had been left behind in Malawi where I had met so many unforgettable people. I just hoped one day I would have a chance to come back to Africa and do something useful.”

But to get back and “do something useful” involved quite an unorthodox passage, particularly as his knowledge emanated from a Master’s degree in agriculture.

Born and brought up in the English county of Surrey, he believes that exploration, investigation and new challenges are part and parcel of his life.

“So when I returned to England only to find that there were no openings for me as a scientist in the agriculture sector, I knew it was time to change direction.”

He came across an advertisement for a laboratory assistant based at Oxford University studying the immune response to HIV infection.

“It immediately caught my eye. The devastating effects had been painfully apparent in Malawi, where high rates of HIV infection were compounded by extreme poverty and a lack of health care. I lost several friends to the disease. At least, I assumed that’s what it was. It wasn’t really talked about.”

Six months after successfully applying for the job, Leslie was offered a position as a PhD student exploring the relationship between HIV and the body’s host cells, trying to understand how HIV manages to avoid being wiped out by our immune systems.

Recently he extended those studies to include the tuberculosis-causing bacteria Mycobacterium tuberculosis (mTB) – a journey that has now brought him to Durban with his wife and two young sons, Samora and Julius.

With the support of a five-year research grant from the KwaZulu-Natal Research Institute, Leslie and a research team’s area of interest will be to try to unbutton the mysteries surrounding the responses made by the immune system cells at the moment HIV and TB pathogens enter the body.

“It’s pretty clear that pathogens like HIV and Myco-bacterium tuberculosis have evolved ways of interfering with this initial signalling, and that allows them to survive. But we need to know a whole lot more.”

The immune system’s Dendritic cells, explains Leslie, are the key to understanding the initial disease battleground.

“They are in the front line of fire, responsible for recognising and signalling the arrival of both HIV and TB. Once we have built up a clearer picture of the key proteins involved in this recognition process and pin down some of the ways in which the invading pathogens are able to modify this interaction to their benefit, we should have some useful data.”

Knowledge gained, he says, could reveal new targets for potential drugs, vaccines, or biological markers of disease that could be helpful for diagnostics.

A three-dimensional model of human tissue that would have been a far-fetched snippet of science fiction a few years ago will play an important role in this unfolding medical story.

Leslie says that thanks to recent advances, it is possible to culture various types of human lung or gut cells in a lab dish and “coax them to organise themselves into structures that are virtually indistinguishable from the natural tissues”.

What does this mean?

“It means that by introducing cells from infected patients into the tissue models we can observe how HIV severely damages the gut mucosa, a process that has been difficult to study in humans. We’ve always had to rely on animal tissue or single cells grown in a laboratory, which behave very differently.”

He also plans to use this technique to investigate the formation and maintenance of TB granulomas. These are the clusters of infected and uninfected cells that form in the lungs of patients as their immune systems attempt to wall off the TB pathogen.

“Granulomas are a hallmark of TB infection, yet whether their formation favours the host or the pathogen, we don’t really know.”

The techniques, he says, don’t require extremely hi-tech equipment.

“You need the expertise – we’ve got that – and you need access to patient samples, which we have in South Africa, and you need an environment that is 100 percent focused on driving the science forward – and that is what the research institute is. It’s exactly the kind of research that should be happening in this part of the world where the effects of TB and HIV are so keenly felt. The aim is to provide data that will be useful in the fight against these diseases. I hope to be part of that incredible journey.”

lizclarke4@gmail.com

***

Front line in body’s battle

Dendritic cells are among the first immune cells to encounter the virus, and are essential in driving an effective immune response.

However, it is becoming increasingly apparent that HIV is able to interfere with this interaction in ways that impair the initial immune response and allow the pathogens to “hide” in reservoirs that medication cannot reach.

In part, this is responsible for the rapid early viral spread and damage to the immune system.

The work in KZN will be done in collaboration with Dr Mattias Svensson of the Karolinska Institute in Sweden and Dr Ben Owens in Oxford, who have developed the lung and gut mucosal models respectively.