title: Immunoevasion and immunosuppression of the macrophage by Mycobacterium tuberculosis.
abstract: By virtue of their position at the crossroads between the innate and adaptive immune response, macrophages play an essential role in the control of bacterial infections. Paradoxically, macrophages serve as the natural habitat to Mycobacterium tuberculosis (Mtb). Mtb subverts the macrophage's mechanisms of intracellular killing and antigen presentation, leading ultimately to the development of tuberculosis (TB) disease. Here, we describe mechanisms of Mtb uptake by the macrophage and address key macrophage functions that are targeted by Mtb-specific effector molecules enabling this pathogen to circumvent host immune response. The macrophage functions described in this review include fusion between phagosomes and lysosomes, production of reactive oxygen and nitrogen species, antigen presentation and major histocompatibility complex class II expression and trafficking, as well as autophagy and apoptosis. All these are Mtb-targeted key cellular pathways, normally working in concert in the macrophage to recognize, respond, and activate 'proper' immune responses. We further analyze and discuss major molecular interactions between Mtb virulence factors and key macrophage proteins and provide implications for vaccine and drug development.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Infection and Immunity Research Center, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Zakaria
authors.initials: Z
authors.lastname: Hmama
authors.forename: Sandra
authors.initials: S
authors.lastname: Peña-Díaz
authors.forename: Sunil
authors.initials: S
authors.lastname: Joseph
authors.forename: Yossef
authors.initials: Y
authors.lastname: Av-Gay
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D001343:Autophagy / Q000276:immunology; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D057131:Immune Evasion; D007108:Immune Tolerance; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D019255:NADPH Oxidases / Q000378:metabolism; D010586:Phagocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D010587:Phagocytosis / Q000276:immunology; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D000949:Histocompatibility Antigens Class II; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases
keywords: bacterial; macrophages; phagocytosis; protein kinases