Gene expression profiling of Mycobacterium tuberculosis Lipoarabinomannan-treated macrophages: A role of the Bcl-2 family member A1 in inhibition of apoptosis in mycobacteria-infected macrophages.
Macrophages play an important role in the establishment of infection by intracellular pathogens. Mycobacterium tuberculosis is known to inhibit apoptosis and to downregulate immune responses of host cells using various strategies, including activation of peroxisome proliferator-activated receptor (PPAR)γ. Mannose-capped lipoarabinomannan (ManLAM) is one of the known bacterial effectors that plays a role in subversion of host immunity and activation of PPARγ. Here, we have used an unbiased global gene expression profiling approach to understand (a) how ManLAM regulates host cell immune responses and (b) the role of PPARγ in modulating ManLAM-induced host cell signaling. We have demonstrated that ManLAM-dependent inhibition of macrophage apoptosis is mediated by the upregulation of the antiapoptotic B-cell CLL/lymphoma 2 (Bcl2) family member A1. Our in silico analyses suggested that ManLAM-mediated PPARγ signaling is linked to important functions such as phagocytosis, cytoskeleton remodeling, cell survival, and autophagy. We have validated that ManLAM upregulates signal transducer and activator of transcription (STAT5)α, an important transcriptional regulator of cell survival in a PPARγ-dependent manner.
Department of Chemistry, Bose Institute, Kolkata, West Bengal, India.
Priyanka
P
Halder
Department of Chemistry, Bose Institute, Kolkata, West Bengal, India.
Ranjeet
R
Kumar
Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India.
Kuladip
K
Jana
Bioinformatics Centre, Bose Institute, Kolkata, West Bengal, India.
Sohini
S
Chakraborty
Bioinformatics Centre, Bose Institute, Kolkata, West Bengal, India.
Zhumur
Z
Ghosh
Department of Chemistry, Bose Institute, Kolkata, West Bengal, India.
Manikuntala
M
Kundu
Department of Chemistry, Bose Institute, Kolkata, West Bengal, India.
Joyoti
J
Basu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D015778:Minor Histocompatibility Antigens; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000502:physiology*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014376:Tuberculosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000382:microbiology
C096816:BCL2-related protein A1; D008070:Lipopolysaccharides; D015778:Minor Histocompatibility Antigens; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C050016:lipoarabinomannan
apoptosis; signaling; tuberculosis