Increased frequency of Myeloid-derived suppressor cells during active tuberculosis and after recent Mycobacterium tuberculosis infection suppresses T-cell function

Rationale: Inadequacy of T-cell responses may result in the development of tuberculosis (TB). Myeloid-derived suppressor cells (MDSCs) have been described as suppressors of T-cell function in cancer biology and recently in several infectious diseases. Objectives: To explore the presence and role of MDSCs in TB. Methods: We analyzed surface markers of MDSCsin peripheral blood and at the site of disease in TB cases and in patients with lung cancer, and in peripheral blood of asymptomatic tuberculin skin test-positive individualswith recent (household) orremote exposure to Mycobacterium tuberculosis (M.tb) and in uninfected healthy control subjects. To evaluate the suppressive capacity of MDSCs, cells of household contacts infected with M.tb and TB cases were isolated and cocultured with CD3+ T cells. Measurements and Main Results: Our results demonstratean increased presence of MDSCs after recent M.tb infectionand disease.Weconfirm their suppression of CD4+ T-cell function, including reduced cytokine responsesandinhibition of CD4+ T-cellproliferation. Only MDSCs from TB cases reduced T-cell activation, altered T-cell trafficking, and suppressed CD8+ T-cell functions. M.tb-expanded MDSCs were associated with significantly higher IL-1β, IL-6, IL-8, granulocyte colony-stimulating factor, and monocyte chemotactic protein-1, and reduced granulocyte-macrophage colony-stimulating factor andmacrophage inflammatory protein-1 beta levels in coculture. Conclusions: These data reveal that innate MDSCs are induced not only during active TB at similar levels as found in cancer, but also in healthy individuals after recent exposure to M.tb. These cells diminish protective T-cell responses and may contribute to the inability of hosts to eradicate the infection and add to the subsequent development of TB disease. Copyright © 2013 by the American Thoracic Society.