EXPRESSION OF VIRULENCE OF MYCOBACTERIUM-TUBERCULOSIS WITHIN HUMAN MONOCYTES - VIRULENCE CORRELATES WITH INTRACELLULAR GROWTH AND INDUCTIONOF TUMOR-NECROSIS-FACTOR-ALPHA BUT NOT WITH EVASION OF LYMPHOCYTE-DEPENDENT MONOCYTE EFFECTOR FUNCTIONS
Rf. Silver et al., EXPRESSION OF VIRULENCE OF MYCOBACTERIUM-TUBERCULOSIS WITHIN HUMAN MONOCYTES - VIRULENCE CORRELATES WITH INTRACELLULAR GROWTH AND INDUCTIONOF TUMOR-NECROSIS-FACTOR-ALPHA BUT NOT WITH EVASION OF LYMPHOCYTE-DEPENDENT MONOCYTE EFFECTOR FUNCTIONS, Infection and immunity, 66(3), 1998, pp. 1190-1199
We assessed the applicability of an in vitro model of low-level infect
ion of human monocytes to the characterization of the virulence of str
ains of the Mycobacterium tuberculosis family. Peripheral blood monocy
tes were infected at a 1:1 ratio with the virulent M. tuberculosis str
ain H37Rv, the avirulent M. tuberculosis strain H37Ra, and the attenua
ted M. bovis strain BCG. Both the percentages of cells infected by the
three strains and the initial numbers of intracellular organisms were
equivalent, as were level of monocyte viability up to 7 days followin
g infection. Intracellular growth reflected virulence, as H37Rv replic
ated in logarithmic fashion throughout the assay, BCG growth reached a
plateau at 4 days, and H37Ra did not grow at all. The same patterns o
f growth were observed following infection of human alveolar macrophag
es with H37Rv and H37Ra. Monocyte production of tumor necrosis factor
alpha was significantly higher following infection with virulent H37Rv
than with either BCG or H37Ra. In contrast, there was no clear correl
ation of interleukin 10 production with virulence. Nonadherent cells o
f purified-protein-derivative-positive donors mediated equivalent degr
ees of reduction of the intracellular growth of H37Rv, BCG, and H37Ra.
Low-level infection of human monocytes with H37Rv, BCG, and H37Ra thu
s provides an in vitro model for assessment of the virulence of these
M. tuberculosis family strains. Furthermore, it is suggested that the
virulence of these strains is expressed primarily by their differing a
bilities to adapt to the intracellular environment of the mononuclear
phagocyte.