Researchers in Belgium have discovered that a type of immune cell previously not well understood helped mice from developing an allergic reaction to certain airborne particles that can trigger asthma: they suggest these cells, called lung interstitial macrophages (IMs), may have the same effect in humans.
The study was the work of Fabrice Bureau and colleagues, at the University of Liège, Belgium, and was published online on 9 November in the Journal of Clinical Investigation.
Our respiratory tract is continually bombarded by microbe-derived molecules. Their arrival triggers numerous immune system responses, and the arrival of one particular molecule, lipopolysaccharide, commonly known as LPS, triggers asthma in some people.
However, what is not well understood is why, when everyone breathes in LPS, doesn’t everyone develop asthma?
In this new study, Bureau and colleagues believe they have discovered an important clue, because in mice they found that lung interstitial macrophages (IMs) prevented lung immune cells known as dendritic cells from triggering a Th2 immune response to LPS and an experimental harmless airborne antigen.
(A Th2 immune response is one that tackles foreign substances outside of cells, whereas Th1 tackles problems inside cells).
The researchers said to the best of their knowledge this was the first time an “in vivo” function has been ascribed to IMs.
They discovered that IMs, but not another type of macrophage known as alveolar macrophages, produced high levels of IL-10 (an anti-inflammatory cytokine) and stopped dendritic cells activated by LPS and loaded with the experimental harmless airborne antigen from maturing and migrating in “an IL-10 dependent manner”, thus preventing the launch of Th2 responses.
To confirm this, they showed that removing IMs from the mice caused them to have “overt asthmatic reactions to innocuous airborne antigens inhaled with low doses of LPS”.
Bureau and colleagues concluded that IMs help prevent airborne LPS from promoting allergy in mice and might play a similar role in humans.
“This study has revealed a crucial role for IMs in maintaining immune homeostasis in the respiratory tract and provides an explanation for the paradox that although airborne LPS has the ability to promote the induction of Th2 responses by lung DCs [dendritic cells], it does not provoke airway allergy under normal conditions,” they wrote.
The researchers suggested future research should focus on whether asthma in humans is caused by inhibiting or disrupting IMs.
“Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice.”
Denis Bedoret, Hugues Wallemacq, Thomas Marichal, Christophe Desmet, Florence Quesada Calvo, Emmanuelle Henry, Rodrigue Closset, Benjamin Dewals, Caroline Thielen, Pascal Gustin, Laurence de Leval, Nico Van Rooijen, Alain Le Moine, Alain Vanderplasschen, Didier Cataldo, Pierre-Vincent Drion, Muriel Moser, Pierre Lekeux, Fabrice Bureau.
J. Clin. Invest., Published online November 9, 2009.
DOI:10.1172/JCI39717
Source: Journal of Clinical Investigation.
Written by: Catharine Paddock, PhD