BAT3 regulates Mycobacterium tuberculosis protein ESAT-6-mediated apoptosis of macrophages.
HLA-B-associated transcript 3 (BAT3), also known as Scythe or BAG6, is a nuclear protein implicated in the control of apoptosis and natural killer (NK) cell-dendritic cell (DC) interaction. We demonstrate that BAT3 modulates the immune response by regulating the function of macrophages. BAT3 is released by macrophages in vitro and it down-regulates nitric oxide and proinflammatory cytokines release in IFN-γ and LPS stimulated macrophages. Furthermore, Mycobacterium tuberculosis-derived protein ESAT-6 (Rv3875) induced transient increase in the expression and release of BAT3 in macrophages. We show that induction of apoptosis by ESAT-6 is dependent on the cleavage of BAT3 by caspase-3 and proteasomal degradation. Our results also indicate that BAT3 regulates ESAT-6-induced apoptosis by interacting with anti-apoptotic protein BCL-2. Taken together, the data suggest that BAT3 plays a role in the early immune response to M. tuberculosis infection and may be a key protein associated with the fate of antigen presenting cells during infection.
Departments of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, United States of America. ajay.grover@colostate.edu
Ajay
A
Grover
Angelo A
AA
Izzo
D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D001426:Bacterial Proteins / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012995:Solubility
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C484266:Bag6 protein, mouse; D061945:Caspase Inhibitors; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D061988:Proteasome Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D053148:Caspase 3; D046988:Proteasome Endopeptidase Complex