title: Interaction of Pattern Recognition Receptors with Mycobacterium Tuberculosis.
abstract: Tuberculosis (TB) is considered a major worldwide health problem with 10 million new cases diagnosed each year. Our understanding of TB immunology has become greater and more refined since the identification of Mycobacterium tuberculosis (MTB) as an etiologic agent and the recognition of new signaling pathways modulating infection. Understanding the mechanisms through which the cells of the immune system recognize MTB can be an important step in designing novel therapeutic approaches, as well as improving the limited success of current vaccination strategies. A great challenge in chronic disease is to understand the complexities, mechanisms, and consequences of host interactions with pathogens. Innate immune responses along with the involvement of distinct inflammatory mediators and cells play an important role in the host defense against the MTB. Several classes of pattern recognition receptors (PRRs) are involved in the recognition of MTB including Toll-Like Receptors (TLRs), C-type lectin receptors (CLRs) and Nod-like receptors (NLRs) linked to inflammasome activation. Among the TLR family, TLR1, TLR2, TLR4, and TLR9 and their down-stream signaling proteins play critical roles in the initiation of the immune response in the pathogenesis of TB. The inflammasome pathway is associated with the coordinated release of cytokines such as IL-1β and IL-18 which also play a role in the pathogenesis of TB. Understanding the cross-talk between these signaling pathways will impact on the design of novel therapeutic strategies and in the development of vaccines and immunotherapy regimes. Abnormalities in PRR signaling pathways regulated by TB will affect disease pathogenesis and need to be elucidated. In this review we provide an update on PRR signaling during M. tuberculosis infection and indicate how greater knowledge of these pathways may lead to new therapeutic opportunities.
authors.affiliation: Division of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Sciences, Utrecht University, Utrecht, The Netherlands.|Cell and Molecular Biology Group, Airways Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Dovehouse Street, London, SW3 6LY, UK.|Clinical Tuberculosis and Epidemiology Research Center, National Research and Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Esmaeil
authors.initials: E
authors.lastname: Mortaz
authors.affiliation: Cell and Molecular Biology Group, Airways Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Dovehouse Street, London, SW3 6LY, UK. ian.adcock@imperial.ac.uk.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Adcock
authors.affiliation: Clinical Tuberculosis and Epidemiology Research Center, National Research and Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Payam
authors.initials: P
authors.lastname: Tabarsi
authors.affiliation: Clinical Tuberculosis and Epidemiology Research Center, National Research and Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Masjedi
authors.affiliation: Chronic Respiratory Diseases Research Center and National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Davood
authors.initials: D
authors.lastname: Mansouri
authors.affiliation: Clinical Tuberculosis and Epidemiology Research Center, National Research and Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Velayati
authors.affiliation: Howard Hughes Medical Institute and St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, 10065, NY, USA.|Paris Descartes Sorbonne Paris Cité University, Imagine Institute, Paris, France.|Laboratory of Human Genetics of Infectious Diseases, INSERM UMR 1163, Imagine Institute, Necker Hospital for Sick Children, Paris, France.|Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France.
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.affiliation: Cell and Molecular Biology Group, Airways Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Dovehouse Street, London, SW3 6LY, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barnes
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000276:immunology; D051379:Mice; D018448:Models, Immunological; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000378:metabolism*; D000683:Serum Amyloid P-Component / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D051193:Toll-Like Receptors / Q000378:metabolism; D014376:Tuberculosis / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D016207:Cytokines; D058847:Inflammasomes; D017382:Reactive Oxygen Species; D051192:Receptors, Pattern Recognition; D000683:Serum Amyloid P-Component; D051193:Toll-Like Receptors; D000099153:Pentraxins
keywords: TLRs; Tuberculosis; inflammasome