Legionella pneumophila is the causative agent of the potentially lethal form of pneumonia called the Legionnaires' disease. Infection is initiated by inhaling aerosols derived from L. pneumophila contaminated water sources, such as cooling towers. Within the lungs, L. pneumophila establishes a specialized niche, termed the Legionella-containing vacuole, in resident alveolar macrophages, which promotes immune protection and bacterial growth. Immunocompromised individuals, the elderly and infants are at increased risk for developing Legionnaires’ disease, but other factors may also contribute to susceptibility in otherwise healthy individuals.
Dietary fibre and its fermentation products, especially short-chain fatty acids (SCFAs), dampen inflammation in a variety of chronic inflammatory diseases, including asthma. The impact of dietary fibre upon host immune responses affects not only the gastrointestinal tract but also peripheral tissues such as the lung. It is thus possible, that dietary fibre may dampen immune responses that prevent Legionella infection.
Here, we investigated the role of the diet and the gut microbiota in Legionella lung infection in mice. We discovered that the short chain fatty acid butyrate, which is secreted in high amounts by commensal bacteria, modulates the transcriptional response of bone marrow derived macrophages (BMDM) during Legionella infection. Surprisingly, butyrate prevents Legionella replication in macrophages by targeting host and bacterial pathways. We are using genetic and biochemical approaches to identify the mechanism by which butyrate affects intracellular Legionella growth. Our data suggest that butyrate inhalation may be useful in combating Legionella infections.