title: A bug's life in the granuloma.
abstract: The granuloma is the defining feature of the host response to infection with Mycobacterium tuberculosis (Mtb). Despite knowing of its existence for centuries, much remains unclear regarding the host and bacterial factors that contribute to granuloma formation, heterogeneity of presentation, and the forces at play within. Mtb is highly adapted to life within the granuloma and employs many unique strategies to both create a niche within the host as well as survive the stresses imposed upon it. Adding to the complexity of the granuloma is the vast range of pathology observed, often within the same individual. Here, we explore some of the many ways in which Mtb crafts the immune response to its liking and builds a variety of granuloma features that contribute to its survival. We also consider the multitude of ways that Mtb is adapted to life in the granuloma and how variability in the deployment of these strategies may result in different fates for both the bacterium and the host. It is through better understanding of these complex interactions that we may begin to strategize novel approaches for tuberculosis treatments.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.|Ragon Institute of Massachusetts General Hospital, Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Constance J
authors.initials: CJ
authors.lastname: Martin
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.|Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Allison F
authors.initials: AF
authors.lastname: Carey
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA. sfortune@hsph.harvard.edu.|Ragon Institute of Massachusetts General Hospital, Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA. sfortune@hsph.harvard.edu.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Fortune
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use; D019175:DNA Methylation; D018450:Disease Progression; D004734:Energy Metabolism; D055354:Exosomes / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006099:Granuloma / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000502:physiology*; D009336:Necrosis; D018384:Oxidative Stress; D010641:Phenotype; D014376:Tuberculosis / Q000150:complications / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*
chemical_list: D000942:Antigens, Bacterial; D000995:Antitubercular Agents
keywords: Granuloma; Macrophage; Phenotypic heterogeneity; Tuberculosis