Detalle de: High-resolution quantitative proteomics applied to the discovery of biomarkers of innate immune response in tuberculosis.

Tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis (MTB). Roughly one third of the world9s 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.