title: Immunomodulation of alveolar epithelial cells by Mycobacterium tuberculosis phosphatidylinositol mannosides results in apoptosis.
abstract: During intracellular residence in macrophages, mycobacterial lipids, namely phosphatidylinositol mannosides (PIM) and lipoarabinomannans, are expelled in the lung milieu to interact with host cells. PIM include a group of essential lipid components of Mycobacterium tuberculosis (M. tb) cell wall. Given that PIM function as mycobacterial adhesins for binding to host cells, the present study explored the consequences of interaction of M. tb PIM with alveolar epithelial cells (AEC). A 24-h PIM exposure at a concentration of 10 μg/mL to AEC conferred cytolysis to AEC via induction of apoptosis, suggesting their potential to alter alveolar epithelium integrity. The results also reflected that type I like AEC are more sensitive to cytolysis than type II AEC. PIM-treated AEC exhibited significant production of reactive oxygen species (ROS) and an immunosuppressive cytokine transforming growth factor-β (TGF-β) in the culture supernatants. Although AEC displayed constitutive mRNA transcripts for toll-like receptors (TLR2 and 4) as well as chemokines (IL-8 and MCP-1), no significant change in their expression was observed upon PIM treatment. Collectively, these results offer insights into PIM potential as M. tb virulence factor that might promote mycobacterial dissemination by causing cytolysis of AEC via increased production of ROS and TGF-β.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Vir
authors.forename: Dheeraj
authors.initials: D
authors.lastname: Gupta
authors.forename: Ritesh
authors.initials: R
authors.lastname: Agarwal
authors.forename: Indu
authors.initials: I
authors.lastname: Verma
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D002460:Cell Line; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D056747:Immunomodulation; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D010716:Phosphatidylinositols / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014397:Tuberculosis, Pulmonary / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D014774:Virulence / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D018925:Chemokines; D016207:Cytokines; D010716:Phosphatidylinositols; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051193:Toll-Like Receptors; D016212:Transforming Growth Factor beta; C034154:phosphatidylinositol mannoside
keywords: Mycobacterium tuberculosis; alveolar epithelial cells; apoptosis; phosphatidylinositol mannosides; transforming growth factor-β