Affiliation:
1. Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland
Abstract
ABSTRACT
To develop a murine model of paucibacillary tuberculosis for experimental chemotherapy of latent tuberculosis infection, mice were immunized with viable
Mycobacterium bovis
BCG by the aerosol or intravenous route and then challenged six weeks later with virulent
Mycobacterium tuberculosis
. The day after immunization, the counts were 3.71 ± 0.10 log
10
CFU in the lungs of aerosol-immunized mice and 3.65 ± 0.11 and 4.93 ± 0.07 log
10
CFU in the lungs and spleens of intravenously immunized mice, respectively. Six weeks later, the lungs of all BCG-immunized mice had many gross lung lesions and splenomegaly; the counts were 5.97 ± 0.14 and 3.54 ± 0.07 log
10
CFU in the lungs and spleens of aerosol-immunized mice, respectively, and 4.36 ± 0.28 and 5.12 ± 0.23 log
10
CFU in the lungs and spleens of intravenously immunized mice, respectively. Mice were then aerosol challenged with
M. tuberculosis
by implanting 2.37 ± 0.13 log
10
CFU in the lungs. Six weeks after challenge,
M. tuberculosis
had multiplied so that the counts were 6.41 ± 0.27 and 4.44 ± 0.14 log
10
CFU in the lungs and spleens of control mice, respectively. Multiplication of
M. tuberculosis
was greatly limited in BCG-immunized mice. Six weeks after challenge, the counts were 4.76 ± 0.24 and 3.73 ± 0.34 log
10
CFU in the lungs of intravenously immunized and aerosol-immunized mice, respectively. In contrast to intravenously immunized mice, there was no detectable dissemination to the spleen in aerosol-immunized mice. Therefore, immunization of mice with BCG by the aerosol route prior to challenge with a low dose of
M. tuberculosis
resulted in improved containment of infection and a stable paucibacillary infection. This model may prove to be useful for evaluation of new treatments for latent tuberculosis infection in humans.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
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