Microbiota: an ally against respiratory infections

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Less well-known than the intestinal microbiota in the digestive field, the impact of the local flora on the pulmonary system was the subject of a study led by a British research team. It seems that certain bacteria from the pulmonary and intestinal microbiota stimulate respiratory immune defenses and protect the host against respiratory infections by promoting the elimination of pathogens.

 

Commensal microbial communities which make up the intestinal or pulmonary microbiota are known for their role as local protectors against pathogens. On the contrary, the mechanisms generating a systemic effect (influence of the intestinal microbiota on the pulmonary sphere, stimulation of the body’s immune response by bacterial groups and their effectors) are still unclear. Thanks to this study, it was possible to analyze them in the context of the most common respiratory infections with Streptococcus pneumoniae and Klebsiella pneumoniae.

Signaling cascade

The objective was to assess the ability to cure a respiratory infection by eliminating the responsible pathogens (S. pneumoniae and K. pneumoniae). One by one, certain known effectors of the immune response in the lungs were blocked or stimulated in order to retrace the signal pathway used to eliminate pathogens. It was observed that the signal is initiated by the stimulation of Nod-like receptors (NLR) by the bacteria Staphylococcus aureus and Staphylococcus epidermidis in the lungs, and by the intestinal microbiota (Lactobacillus reuteri, Enterococcus faecalis, Lactobacillus crispatus and Clostridium orbiscindens). The response to infection is regulated by these bacteria through interleukin-17A (a cytokine mainly produced by CD4 T helper cells), which in turn activates the production of granulocyte-macrophage colony-stimulating factors (GM-CSF). The following signal pathway was identified: microbiota and GM-CSF work together to produce alveolar macrophages which then kill the pathogens responsible for the infection.

A wide field of action

In addition to the digestive system, the lungs also take advantage of the protective effect of the intestinal microbiota thanks to complex mechanisms whose signal is the GM-CSF.  However, it is considered that the central coordinator of the immune homeostasis is the stimulation of Nod-like receptors by the microbiota. These results are promising and suggest that a simple bacterial consortium, i.e. well-defined bacterial groups, could grant a protection equivalent to that provided by the complex community of the microbiota. The study confirms the results of other works underlining the significant role of the intestinal microbiota in the fight against respiratory infections and identifies the involved protective bacteria. It thus lays the groundwork for future cross-sectional studies allowing for a better management of respiratory infections, which remain one of the leading causes of death.

 

Sources:

The microbiota protects against respiratory infection via GM-CSF signaling | Nature Communications. Available at: https://www.nature.com/articles/s41467-017-01803-x. (Accessed: 30th January 2018)