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Infection and Immunity, August 2002, p. 4501-4509, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4501-4509.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Dissemination of Mycobacterium tuberculosis Is Influenced by Host Factors and Precedes the Initiation of T-Cell Immunity

Alissa A. Chackerian, Jennifer M. Alt, Thushara V. Perera, Christopher C. Dascher, and Samuel M. Behar*

Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115

Received 24 January 2002/ Returned for modification 21 March 2002/ Accepted 6 May 2002

We report that dissemination of Mycobacterium tuberculosis in the mouse is under host control and precedes the initiation of T-cell immunity. Nine to eleven days after aerosol inoculation, M. tuberculosis disseminates to the pulmonary lymph nodes (LN), where M. tuberculosis-specific T cells are detected 2 to 3 days thereafter. This indicates that the initial spread of bacteria occurs via lymphatic drainage and that the acquired T-cell immune response is generated in the draining LN. Dissemination to peripheral sites, such as the spleen and the liver, occurs 11 to 14 days postinfection and is followed by the appearance of M. tuberculosis-specific T cells in the lung and the spleen. In all cases studied, dissemination to the LN or the spleen preceded activation of M. tuberculosis-specific T cells in that organ. Interestingly, bacteria disseminate earlier from the lungs of resistant C57BL/6 mice than from the lungs of susceptible C3H mice, and consequently, C57BL/6 mice generate an immune response to M. tuberculosis sooner than C3H mice generate an immune response. Thus, instead of spreading infection, early dissemination of M. tuberculosis may aid in the initiation of an appropriate and timely immune response. We hypothesize that this early initiation of immunity following inoculation with M. tuberculosis may contribute to the superior resistance of C57BL/6 mice.

* Corresponding author. Mailing address: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Smith Building, Room 516C, One Jimmy Fund Way, Boston, MA 02115. Phone: (617) 525-1033. Fax: (617) 525-1010. E-mail: sbehar{at}rics.bwh.harvard.edu.

Editor: R. N. Moore

Infection and Immunity, August 2002, p. 4501-4509, Vol. 70, No. 8
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.8.4501-4509.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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