Tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis (MTB). Roughly one third of the world's population carries MTB in a dormant form. TB is responsible for the death of more than 1.8 million people each year. EMI-TB (Eliciting mucosal immunity in TB) is an EU Horizon2020 funded action focused on selecting and developing a novel vaccine candidate for TB. Our specific aim (CSIC, Vigo, Spain) is to establish a panel of protein biomarkers representative of those individuals that had been in contact with a patient with microbiological confirmed pulmonary TB but did not get infected. Samples (serum, saliva and sputum) were collected from volunteer patients (TB: pulmonary TB; LTBI: contacts with latent TB infection; non-LTBI: contacts without evidence of latent TB infection). Quantitative proteomics were done using TMT10plex (Thermo) and a LC-Orbitrap Elite platform. Modulated proteins were selected after exhaustive manual review of the processed data and non-parametric statistical analysis with R software. We have found a unique proteomic signature in the sputum of non-LTBI contacts, consisting in a set of 32 proteins mainly involved in regulation of endopeptidase activity, defense against pathogens and perception of bitter taste. This suggests that nasal and oral mucosa play a critical role in the initial entry of the pathogen in the host, opening a new window for eliciting the mucosal immunity to enhance the innate immune response as the first barrier to fight infection. We are starting a validation in a functional model of MTB infection in order to test the biological and clinical significance of our findings.

Peer reviewed