Human Lung Hydrolases Delineate Mycobacterium tuberculosis–Macrophage Interactions and the Capacity To Control Infection

Abstract

Pulmonary surfactant contains homeostatic and antimicrobial hydrolases. When Mycobacterium tuberculosis is initially deposited in the terminal bronchioles and alveoli, as well as following release from lysed macrophages, bacilli are in intimate contact with these lung surfactant hydrolases. We identified and measured several hydrolases in human alveolar lining fluid and lung tissue that, at their physiological concentrations, dramatically modified the M. tuberculosis cell envelope. Independent of their action time (15 min to 12 h), the effects of the hydrolases on the M. tuberculosis cell envelope resulted in a significant decrease (60–80%) in M. tuberculosis association with, and intracellular growth of the bacteria within, human macrophages. The cell envelope-modifying effects of the hydrolases also led to altered M. tuberculosis intracellular trafficking and induced a protective proin-flammatory response to infection. These findings add a new concept to our understanding of M. tuberculosis–macrophage inter-actions (i.e., the impact of lung surfactant hydrolases on M. tuberculosis infection).

Pathology and immune reactivity: understanding multidimensionality in pulmonary tuberculosis

“…However, interactions of the bacilli with respiratory epithelial cells modulate abundance of cytokines and distinct enzymes, such as cognates of the matrix metalloproteinase (MMP) family [76], arginase-1 [77], and indoleamine 2,3-dioxygenase-1 (IDO-1) [78]. Moreover, by releasing lung hydrolases and additional enzymes into the alveolar lining fluid, pneumocytes can modify the bacterial envelop [79] and limit Mtb's entry into myeloid cells.…”

The innate immune response in human tuberculosis

“…Surfactant proteins (members of the collectin family) bind to Mtb, causing agglutination (Ferguson et al ., 1999) and enhanced phagocytosis by macrophages (Gaynor et al ., 1995). Secreted hydrolases can alter the cell wall of Mtb and affect interactions with macrophages and host immune responses (Arcos et al ., 2011). …”

Broadening Our View About the Role of Mycobacterium tuberculosis Cell Envelope Components During Infection: A Battle for Survival

“…Although, Nod2 can synergize with TLR-signaling pathways enhancing pro-inflammation (Ferwerda et al, 2005), its capacity to interfere/associate with phagocytic receptor trafficking networks is not well established. As cytosolic Nod2 appears to be associated with intracellular vesicles , its role in triggering pro-inflammation may depend on vesicular fusion events controlled during M.tb phagocytosis and phagosomal maturation (Sasindran & Torrelles, 2011 …”

“…Collectins such as surfactant protein -A and -D, and mannose binding protein, and their specific receptors have been shown to be important in M.tb recognition by the host; and their contribution in M.tb pathogenesis is discussed elsewhere (Sasindran & Torrelles, 2011;Torrelles et al, 2008a). Other receptors involved in the recognition of M.tb and inflammation are CD14, scavenger receptor-A, Fc-receptor, Mincle, and Dectin-1 (Sasindran & Torrelles, 2011).…”

“…Other receptors involved in the recognition of M.tb and inflammation are CD14, scavenger receptor-A, Fc-receptor, Mincle, and Dectin-1 (Sasindran & Torrelles, 2011). CD14 (Khanna et al, 1996) and the scavenger receptor SR-A (Zimmerli et al, 1996), are shown to participate in the uptake of nonopsonized bacilli by tissue-specific macrophages; where their role in inflammation varies depending on the species-specific cell type used.…”