PUBLICATION

Superinfecting mycobacteria home to established tuberculous granulomas

Authors
Cosma, C.L., Humbert, O., and Ramakrishnan, L.
ID
ZDB-PUB-070212-3
Date
2004
Source
Nature immunology   5(8): 828-835 (Journal)
Registered Authors
Cosma, Christine, Humbert, Jasper, Ramakrishnan, Lalita
Keywords
none
MeSH Terms
  • Animals
  • Disease Models, Animal
  • Gene Products, gag/biosynthesis
  • Granuloma/immunology*
  • Liver/immunology
  • Liver/microbiology
  • Liver/pathology
  • Lung/immunology
  • Lung/microbiology
  • Lung/pathology
  • Mycobacterium Infections, Nontuberculous/immunology*
  • Mycobacterium marinum/immunology
  • Rana pipiens
  • Salmonella Infections/immunology
  • Salmonella arizonae/immunology
  • Spleen/immunology
  • Spleen/microbiology
  • Spleen/pathology
  • Superinfection/immunology*
  • Tuberculosis/immunology*
  • Tuberculosis/pathology
  • Zebrafish
PubMed
15220915 Full text @ Nat. Immunol.
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping