title: Interferon-Gamma Improves Macrophages Function against M. tuberculosis in Multidrug-Resistant Tuberculosis Patients.
abstract: Background. Mycobacterium tuberculosis (M. tuberculosis) that causes tuberculosis (TB) kills millions of infected people annually especially multidrug-resistant tuberculosis (MDR-TB). On infection, macrophages recognize the mycobacteria by toll-like receptor (TLR) followed by phagocytosis and control of mycobacteria. In addition, macrophages also secrete IL-12 to induce IFN-γ production by T, which, in turn, increases the phagocytosis and oxidative burst. Individuals with defects in innate or adaptive immunity exhibit increased susceptibility to M. tuberculosis. Understanding these immunologic mechanisms will help in TB control. We aimed to investigate the immunopathologic mechanisms in MDR-TB and role of recombinant human interferon-gamma (rhIFN-γ). Study Design and Methods. Monocyte-derived macrophages (MDMs) were generated from peripheral blood mononuclear cells of MDR-TB patients and healthy subjects and were investigated for immunologic response by ELISA and flow cytometry. Results. Different functional and molecular anomalies were observed in macrophages. In addition, a defective immune response to M. tuberculosis from the patient's MDMs was characterized, which in turn improved by pretreatment with rhIFN-γ. Conclusion. This work highlights the fact that rhIFN-γ improves macrophages function against M. tuberculosis and treatment of patients with poor responsiveness to TB therapy may be needed in future to include IFN-γ as adjuvant therapy after the full characterization of pathological and molecular mechanisms in these and in other more multidrug-resistant TB patients.
authors.affiliation: Department of Microbiology, Kohat University of Science and Technology, KPK, Kohat 26000, Pakistan.
authors.forename: Taj Ali
authors.identifier: 0000-0002-0851-0422
authors.initials: TA
authors.lastname: Khan
authors.affiliation: Department of Microbiology, Kohat University of Science and Technology, KPK, Kohat 26000, Pakistan.
authors.forename: Humaira
authors.initials: H
authors.lastname: Mazhar
authors.affiliation: Department of Biotechnology, Kohat University of Science and Technology, KPK, Kohat 26000, Pakistan.
authors.forename: Shamim
authors.identifier: 0000-0002-1332-0666
authors.initials: S
authors.lastname: Saleha
authors.affiliation: Department of Immunology, Armed Forces Institute of Pathology, Rawalpindi 46000, Pakistan.
authors.forename: Hamid Nawaz
authors.identifier: 0000-0003-0105-103X
authors.initials: HN
authors.lastname: Tipu
authors.affiliation: Department of Microbiology, Kohat University of Science and Technology, KPK, Kohat 26000, Pakistan.
authors.forename: Niaz
authors.initials: N
authors.lastname: Muhammad
authors.affiliation: Department of Microbiology, Kohat University of Science and Technology, KPK, Kohat 26000, Pakistan.
authors.forename: Muhammad Nasser
authors.initials: MN
authors.lastname: Abbas