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1 July 2005

Volume 192, Number 1
The Journal of Infectious Diseases 2005;192:89–97
© 2005 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2005/19201-0014$15.00
DOI: 10.1086/430621
MAJOR ARTICLE

Differential Organization of the Local Immune Response in Patients with Active Cavitary Tuberculosis or with Nonprogressive Tuberculoma

Timo Ulrichs,1,2

George A. Kosmiadi,3

Sabine Jörg,1

Lydia Pradl,1

Marina Titukhina,4

Vladimir Mishenko,3

Nadya Gushina,3 and

Stefan H. E. Kaufmann1

1Department of Immunology, Max‐Planck‐Institute for Infection Biology, and 2Department of Medical Microbiology and Infection Immunology, Institute for Infection Medicine, Charité University Medicine, Campus Benjamin Franklin, Berlin, Germany; Departments of 3Immunology and 4Thoracic Surgery, Central Tuberculosis Research Institute, Moscow, Russian Federation

Background.In 90% of all cases, Mycobacterium tuberculosis infection results in latency rather than active disease, with the pathogen being contained within granulomatous lesions at the site of primary infection. Failure of this containment leads to reactivation of postprimary tuberculosis (TB). The regional immune processes that sustain the delicate balance with persistent M. tuberculosis, however, remain unclear.

Methods.We compared activation statuses, biological functions, and interactions of host immune cells in human nonprogressive tuberculoma and active cavitary tuberculous lung tissue.

Results.Dissection of early granuloma formations revealed differential cellular distribution and activation statuses of distinct cell types in different regions relative to the central caseotic caverna or the tuberculoma in tuberculous lung tissue. In patients with tuberculoma with latent infection, distant parts of lung tissue exhibited strong vascularization and profound proliferative activity, indicating that continuous immune defense is required for mycobacterial containment, which is absent in cavitary tuberculous lung lesions.

Conclusions.We conclude that differential regulation of the local immune response is crucial for the containment of M. tuberculosis and that a continuous antigen‐specific cross talk between the host immune system and M. tuberculosis is ensured during latency. This activation requires sufficient supply of nutrients and well‐coordinated structural organization, both of which are lost during reactivation of TB.

Received 17 November 2004; accepted 1 February 2005; electronically published 27 May 2005.

Reprints or correspondence: Dr. Timo Ulrichs, Max‐Planck‐Institute for Infection Biology, Schumannstr. 21/22, 10117 Berlin, Germany ().

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  • Financial support: European Union Framework Program 6 (to S.H.E.K. and T.U.); Bundesministerium für Bildung und Firschung, competence networks on “Pathogenomics” and “Structural Genomics of M. tuberculosis” (to S.H.E.K.).

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