title: Mycobacterium tuberculosis and Human Immunodeficiency Virus Type 1 Cooperatively Modulate Macrophage Apoptosis via Toll Like Receptor 2 and Calcium Homeostasis.
abstract: The emergence of drug resistant strains of Mycobacterium tuberculosis (M. tuberculosis) together with reports of co-infections with the human immunodeficiency virus (HIV) has renewed interest to better understand the intricate mechanisms prevalent during co-infections. In this study we report a synergistic effect of M. tuberculosis and HIV-1, and their antigens Rv3416 and Nef, respectively, in inhibiting apoptosis of macrophages. This inhibition involves the TLR2 pathway and second messengers that play complementing and contrasting roles in regulating apoptosis. Interestingly, the route of calcium influx into cells differentially regulates apoptosis during antigenic co-stimulation. While calcium released from intracellular stores was anti-apoptotic, calcium influx from the external milieu was pro-apoptotic. Further, molecular sensors of intracellular calcium release aid in antigen mediated inhibition of apoptosis. A cross-regulation between oxidative burst and differential routing of calcium influx governed apoptosis. Interestingly, the HIV-1 Nef supported anti-apoptotic responses in macrophages whereas Vpu had no significant effect. These results point to a synergistic liaison between M. tuberculosis and HIV-1 in regulating macrophage apoptosis.
authors.affiliation: Infectious Disease Immunology Lab, Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi 110007, India.
authors.forename: Subhash
authors.initials: S
authors.lastname: Mehto
authors.affiliation: Infectious Disease Immunology Lab, Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi 110007, India.
authors.forename: Cecil
authors.initials: C
authors.lastname: Antony
authors.affiliation: Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Nabab
authors.initials: N
authors.lastname: Khan
authors.affiliation: Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Arya
authors.affiliation: Infectious Disease Immunology Lab, Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi 110007, India.
authors.forename: Arti
authors.initials: A
authors.lastname: Selvakumar
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India.
authors.forename: Brijendra K
authors.initials: BK
authors.lastname: Tiwari
authors.affiliation: Infectious Disease Immunology Lab, Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi 110007, India.
authors.forename: Mohit
authors.initials: M
authors.lastname: Vashishta
authors.affiliation: CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India.
authors.forename: Yogendra
authors.initials: Y
authors.lastname: Singh
authors.affiliation: Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Shahid
authors.initials: S
authors.lastname: Jameel
authors.affiliation: Infectious Disease Immunology Lab, Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi 110007, India.
authors.forename: Krishnamurthy
authors.initials: K
authors.lastname: Natarajan
mesh_terms: D000941:Antigens / Q000378:metabolism; D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D060085:Coinfection; D045304:Cytochromes c / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D015658:HIV Infections / Q000150:complications; D015497:HIV-1; D006706:Homeostasis; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology / Q000821:virology; D053078:Membrane Potential, Mitochondrial; D009169:Mycobacterium tuberculosis; D034741:RNA, Small Interfering / Q000378:metabolism; D016897:Respiratory Burst; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D014376:Tuberculosis / Q000150:complications; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D000941:Antigens; D001426:Bacterial Proteins; D034741:RNA, Small Interfering; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D045304:Cytochromes c; D002118:Calcium