High-resolution quantitative proteomics applied to the study of the specific protein signature in the sputum and saliva of active tuberculosis patients and their infected and uninfected contacts.

Our goal was to establish panels of protein biomarkers that are characteristic of patients with microbiologically confirmed pulmonary tuberculosis (TB) and their contacts, including latent TB-infected (LTBI) and uninfected patients. Since the first pathogen-host contact occurs in the oral and nasal passages the saliva and sputum were chosen as the biological fluids to be studied. Quantitative shotgun proteomics was performed using a LTQ-Orbitrap-Elite platform. For active TB patients, both fluids exhibited a specific accumulation of proteins that were related to complement activation, inflammation and modulation of immune response. In the saliva of TB patients, a decrease of in proteins related to glucose and lipid metabolism was detected. In contrast, the sputum of uninfected contacts presented a specific proteomic signature that was composed of proteins involved in the perception of bitter taste, defense against pathogens and innate immune response, suggesting that those are key events during the initial entry of the pathogen in the host. SIGNIFICANCE: This is the first study to compare the saliva and sputum from active TB patients and their contacts. Our findings strongly suggest that TB patients show not only an activation of processes that are related to complement activation and modulation of inflammation but also an imbalance in carbohydrate and lipid metabolism. In addition, those individuals who do not get infected after direct exposure to the pathogen display a typical proteomic signature in the sputum, which is a reflection of the secretion from the nasal and oral mucosa, the first immunological barriers that M. tuberculosis encounters in the host. Thus, this result indicates the importance of the processes related to the innate immune response in fighting the initial events of the infection.