Nature Immunology
5, 828 - 835 (2004)
Published online: 27 June 2004; | doi:10.1038/ni1091
Superinfecting mycobacteria home to established tuberculous granulomasChristine L Cosma1, Olivier Humbert1
& Lalita Ramakrishnan1, 2, 31
Department of Microbiology, University of Washington School of Medicine, Box 357242, Seattle, Washington 98195, USA. 2
Department of Immunology, University of Washington School of Medicine, Box 357242, Seattle, Washington 98195, USA. 3
Department of Medicine, University of Washington School of Medicine, Box 357242, Seattle, Washington 98195, USA.
Correspondence should be addressed to Lalita Ramakrishnan lalitar@u.washington.eduA 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.
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