title: Interaction of alveolar epithelial cells with CFP21, a mycobacterial cutinase-like enzyme.
abstract: Mycobacterium tuberculosis (M. tb), an intracellular pathogen, has the ability to infect alveolar epithelial cells (AEC) also in addition to alveolar macrophages. The virulence of M. tb is attributed to proteins encoded by genomic regions of deletion (RD) and till date 16 such regions (RD1-RD16) have been identified. Culture filtrate protein 21 (CFP21), a RD2 secretory protein, is a cutinase-like enzyme that possesses esterase and lipolytic activity. It is hypothesized that CFP21 could be playing a role in M. tb virulence by disrupting the host cell integrity. In this study, recombinant CFP21 was expressed and purified. The in vitro exposure of type I (WI26) and type II (A549) AEC to CFP21 resulted in a significant decline in their cellular viability by inducing cell apoptosis. However, the cytotoxic effects were more pronounced in WI26 cells than in A549 cells. The analysis of immune responses in CFP21-treated AEC exhibited significant production of reactive oxygen species and anti-inflammatory cytokine TGF-β which indicated oxidative stress-mediated cell death. These results show that CFP21 could play an important role in M. tb pathogenesis by disrupting the host alveolar barrier and thereby facilitating mycobacterial dissemination.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Sector-12, Chandigarh, 160012, 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: D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D054884:Host-Pathogen Interactions; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; C113719:CFP21 protein, Mycobacterium tuberculosis; D018925:Chemokines; D016207:Cytokines; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D051193:Toll-Like Receptors; D009569:Nitric Oxide; D002265:Carboxylic Ester Hydrolases; C019952:cutinase
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