Microbiota educates innate immune response to Toll-like receptors stimulation and RSV infection in lung

Since the apparition of new technologies permitting the precise characterization of microorganisms, studies involving microbiotas’ influence swarmed in the literature. It has also brought evidences to raise the emerging concept that the lung is not a sterile compartment and possesses its own microbiota. It has been shown that the lung microbiota could be altered in patients suffering of respiratory diseases, such as asthma or bronchiolitis caused by respiratory syncytial virus (RSV). Microbiota is an important partner at the interface between immune cells and epithelium, which contribute to shaping efficient and safe defenses. In this study, we postulate that endogenous microbiota could dampen an excessive reactivity of the lung tissue to external stimuli. First, using lung explants from specific pathogen free (SPF) and germ-free (GF) mice exposed to Toll-like receptors (TLRs) ligands or RSV, we show a higher production of pro-inflammatory cytokines, notably IL-6 and TNFα by lung explants from GF mice compared to SPF mice. These data suggest that microbiota educates innate immune response in lung by reducing pro-inflammatory pathways. We have also observed a more abundant expression of TLR4 in the lungs of GF mice compared to SPF mice, which could predispose the innate immune system of GF mice to react strongly to environmental stimuli. In this context, the microbiota seems to reduce innate immune receptors reactivity. Not only these data illustrate how the microbiota educates the innate immune system, but they also contribute to the emerging concept of immunomodulation by probiotics bacteria to prevent respiratory pathology.