title: Superinfecting mycobacteria home to established tuberculous granulomas.
abstract: A central paradox of tuberculosis immunity is that reinfection and bacterial persistence occur despite vigorous host immune responses concentrated in granulomas, which are organized structures that form in response to infection. Prevailing models attribute reinfection and persistence to bacterial avoidance of host immunity via establishment of infection outside primary granulomas. Alternatively, persistence is attributed to a gradual bacterial adaptation to evolving host immune responses. We show here that superinfecting Mycobacterium marinum traffic rapidly into preexisting granulomas, including their caseous (necrotic) centers, through specific mycobacterium-directed and host cell-mediated processes, yet adapt quickly to persist long term therein. These findings demonstrate a failure of established granulomas, concentrated foci of activated macrophages and antigen-specific immune effector cells, to eradicate newly deposited mycobacteria not previously exposed to host responses.
authors.affiliation: Department of Microbiology, University of Washington School of Medicine, Box 357242, Seattle, Washington 98195, USA.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Cosma
authors.forename: Olivier
authors.initials: O
authors.lastname: Humbert
authors.forename: Lalita
authors.initials: L
authors.lastname: Ramakrishnan
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015683:Gene Products, gag / Q000096:biosynthesis; D006099:Granuloma / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D009165:Mycobacterium Infections, Nontuberculous / Q000276:immunology*; D019910:Mycobacterium marinum / Q000276:immunology; D011894:Rana pipiens; D012480:Salmonella Infections / Q000276:immunology; D012476:Salmonella arizonae / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D015163:Superinfection / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000473:pathology; D015027:Zebrafish
chemical_list: D015683:Gene Products, gag