Macrophages to protect you from asthma

April 17, 2017 Sponsored Press Release

It has long been known that exposure to microbes can play a protective role against the subsequent development of asthma. However, the mechanisms underlying this so-called “hygiene” hypothesis remain poorly understood. Researchers from GIGA of the University of Liège provide an explanation and propose to use this discovery to set up a strategy of cell therapy to treat asthma in humans. Their discovery is published in Immunity.

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The incidence of asthma is increasing steadily, especially in developed countries. One of the reasons given for this rise is the excessive level of hygiene in our environment. Epidemiological studies have indeed shown that exposure to a so-called “non-hygienic” environment, rich in microbes, plays a protective role against the development of allergies and asthma. Conversely, an overly hygienic environment would predispose an individual to asthma, although the reasons are not known. In allergic reactions such as asthma, the immune system does not function properly and responds exaggeratedly to harmful allergens present in the environment (pollens, mites, etc.). In an article published in Immunity, researchers at the University of Liège show that exposure to bacterial DNA (one of the microbial compounds) drastically amplifies a population of pulmonary macrophages and makes them strongly immunosuppressive, which prevents and treats asthma in mice. This discovery offers promising prospects for the development of a cell therapy based on the administration of these regulatory macrophages to asthmatic patients.

Are we too clean?

Under the guidance of Fabrice Bureau, professor at ULG and invesetigator at Welbio, and Thomas Marichal, research associate of the F.R.S.-FNRS, the scientific team has discovered how a non-hygienic environment, rich in bacterial DNA, helps to protect against asthma. Notably, synthetic compounds mimicking bacterial DNA have been tested in other studies in humans for their therapeutic effect in the treatment of asthma, but until now none of these compounds have been approved on the market. This may be due to their toxicity or the lack of basic knowledge about their mechanisms of action. Here, the mechanisms of action have been identified. This study allows a cell therapy approach that would avoid the use of potentially toxic compounds.

If it is possible to create a suppressive macrophage from blood monocytes of asthmatic patients, it is quite conceivable to reinject these macrophages into the lungs.

In this study in mice, researchers first looked at how exposure to microbial compounds (such as bacterial wall components or their own DNA) or whole microbes would modify the immune environment of the lung. They found that bacterial DNA, unlike the other compounds, was able to strongly amplify a population of so-called interstitial macrophages and that this expansion persisted for several months in the individual.

Surprisingly, if these same macrophages were isolated from a mouse and re-injected into the lungs of a naive recipient mouse, such individual was not capable of developing asthma against house dust mite extracts. Similarly, if these macrophages were transferred to an asthmatic mouse, the asthmatic mouse was cured, and no more symptoms of asthma were present. Based on these results, the researchers now envision “making” macrophages with similar properties in vitro from monocytes, a white blood cell type found in the human blood.

“If it is possible to create a suppressive macrophage from blood monocytes of asthmatic patients, it is quite conceivable to reinject these macrophages into the lungs of these same patients, during routine bronchoscopy procedures performed by pneumologists here at the CHU, and to evaluate the therapeutic potential of these cells,”  concludes Bureau.

The researchers have just filed a patent  to protect their results and invention and are going to initiate studies in humans.

Sabatel, Catherine et al., Exposure to Bacterial CpG DNA Protects from Airway Allergic Inflammation by Expanding Regulatory Lung Interstitial Macrophages, Immunity, 2017, Volume 46 , Issue 3 , 457 – 473

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