title: Infergen Stimulated Macrophages Restrict Mycobacterium tuberculosis Growth by Autophagy and Release of Nitric Oxide.
abstract: IFN alfacon-1 (Infergen) is a synthetic form of Interferon (IFN)-α2b. Infergen has immunomodulatory activity and is effective against hepatitis C virus. However, the effect of Infergen (IFG) on Mycobacterium tuberculosis (Mtb) has not yet been reported. Therefore, for the first time, we have studied the influence of IFG in constraining the survival of Mtb in human macrophages. We observed that IFG significantly enhanced the maturation and activation of macrophages. Further, it substantially augmented the secretion of IL-6, nitric oxide (NO) and antigen uptake. Moreover, macrophages exhibited remarkably higher bactericidal activity, as evidenced by reduction in the Mtb growth. Infergen-mediated mechanism was different from the type-1 interferons; since it worked through the activation of NF-κB, phosphorylation of STAT-3 and Akt-PI3K that improved the bactericidal activity through autophagy and NO release. In future, IFG immunotherapy can be a novel strategy for treating patients and controlling TB.
authors.affiliation: Immunology Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, 160036, India.|Department of Biotechnology, Panjab University, Chandigarh, 160014, India.
authors.forename: Susanta
authors.initials: S
authors.lastname: Pahari
authors.affiliation: Immunology Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, 160036, India.
authors.forename: Nargis
authors.initials: N
authors.lastname: Khan
authors.affiliation: Immunology Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, 160036, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Aqdas
authors.affiliation: Immunology Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, 160036, India.
authors.forename: Shikha
authors.initials: S
authors.lastname: Negi
authors.affiliation: Department of Biotechnology, Panjab University, Chandigarh, 160014, India.
authors.forename: Jagdeep
authors.initials: J
authors.lastname: Kaur
authors.affiliation: Immunology Laboratory, CSIR-Institute of Microbial Technology, Chandigarh, 160036, India.
authors.forename: Javed N
authors.initials: JN
authors.lastname: Agrewala
mesh_terms: D001343:Autophagy; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008264:Macrophages / Q000166:cytology*; D018613:Microscopy, Confocal; D009169:Mycobacterium tuberculosis; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology; D000074084:THP-1 Cells; D014376:Tuberculosis / Q000276:immunology* / Q000628:therapy*; D019323:omega-N-Methylarginine / Q000737:chemistry
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D016207:Cytokines; D006684:HLA-DR Antigens; C508600:IL6 protein, human; D016898:Interferon-alpha; D015850:Interleukin-6; D011994:Recombinant Proteins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C050739:interferon alfacon-1; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II