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*
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021;
Tuberculosis Research Section, LHD, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852; and
Institute for the Study of Human Bacterial Pathogenesis, Department of Pathology, Baylor College of Medicine, Houston, TX 77030
Mycobacterium tuberculosis CDC1551, a clinical
isolate reported to be hypervirulent and to grow faster than other
isolates, was compared with two other clinical isolates (HN60 and
HN878) and two laboratory strains (H37Rv and Erdman). The initial
(1–14 days) growth of CDC1551, HN60, HN878, and H37Rv was similar in
the lungs of aerosol-infected mice, but growth of Erdman was slower.
Thereafter, the growth rate of CDC1551 decreased relative to the other
strains which continued to grow at comparable rates up to day 21. In
the lungs of CDC1551-infected mice, small well-organized granulomas
with high levels of TNF-
, IL-6, IL-10, IL-12, and IFN-
mRNA were
apparent sooner than in lungs of mice infected with the other strains.
CDC1551-infected mice survived significantly longer. These findings
were confirmed in vitro. The growth rates of H37Rv and CDC1551 in human
monocytes were the same, but higher levels of TNF-, IL-10, IL-6, and
IL-12 were induced in monocytes after infection with CDC1551 or by
exposure of monocytes to lipid fractions from CDC1551. CD14 expression
on the surface of the monocytes was up-regulated to a greater extent by
exposure to the lipids of CDC1551. Thus, CDC1551 is not more virulent
than other M. tuberculosis isolates in terms of growth
in vivo and in vitro, but it induces a more rapid and robust host
response.
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C. Manca, L. Tsenova, A. Bergtold, S. Freeman, M. Tovey, J. M. Musser, C. E. Barry III, V. H. Freedman, and G. Kaplan Virulence of a Mycobacterium tuberculosis clinical isolate in mice is determined by failure to induce Th1 type immunity and is associated with induction of IFN-alpha /beta PNAS, May 8, 2001; 98(10): 5752 - 5757. [Abstract] [Full Text] [PDF]
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