Intragranulomatous necrosis in pulmonary granulomas is not related to resistance against Mycobacterium tuberculosis infection in experimental murine models induced by aerosol.

Intragranulomatous necrosis is a primary feature in the natural history of human tuberculosis (TB). Unfortunately, this phenomenon is not usually seen in the experimental TB murine model. Artificial induction of this necrosis in pulmonary granulomas (INPG) may be achieved through aerosol inoculation of lipopolysaccharide (LPS) 3 weeks after Mycobacterium tuberculosis infection.

Intragranulomatous necrosis in lungs of mice infected by aerosol with Mycobacterium tuberculosis is related to bacterial load rather than to any one cytokine or T cell type.

Low dose aerosol infection of C57BL/6 mice with a clinical strain of Mycobacterium tuberculosis (UTE 0335 R) induced intragranulomatous necrosis in pulmonary granulomas (INPG) at week 9 postinfection. Infection of different knockout (KO) mouse strains with UTE 0335 R induced INPG in all strains and established two histopathological patterns. The first pattern was seen in SCID mice and in mice with deleted alpha/beta T receptor, TNF R1, IL-12, IFN-gamma, or iNOS genes, and showed a massive INPG with a high granulomatous infiltration of the lung, a large and homogeneous eosinophilic necrosis full of acid-fast bacilli, with marked karyorrhexis, coarse basophilic necrosis, and surrounded by patches delimited by partially conserved alveolar septum full of PMNs.

Association between the infectivity of Mycobacterium tuberculosis strains and their efficiency for extrarespiratory infection.

Extrarespiratory tuberculosis is determined mainly by impaired immunity of the host. The additional role played by bacterial factors in determining whether an infection by Mycobacterium tuberculosis disseminates to extrarespiratory sites has not been analyzed in depth. In the present study, we selected patients who were dually infected with 2 M.

Immunotherapy with fragmented Mycobacterium tuberculosis cells increases the effectiveness of chemotherapy against a chronical infection in a murine model of tuberculosis.

Reduction of colony forming units by rifampicin-isoniazid therapy given 9-17 weeks post-infection was made more pronounced by immunotherapy with a vaccine made of fragmented Mycobacterium tuberculosis cells detoxified and liposomed (RUTI), given on weeks 17, 19 and 21 post-infection, in the murine model of tuberculosis in C57BL/6 and DBA/2 inbred strains. RUTI triggered a Th1/Th2 response, as demonstrated by the production of IgG1, IgG2a and IgG3 antibodies against a wide range of peptides. The histological analysis did not show neither eosinophilia nor necrosis, and granulomatous infiltration was only slightly increased in C57BL/6 mice when RUTI was administered intranasally.

Catalase-peroxidase activity has no influence on virulence in a murine model of tuberculosis.

The capacity to generate a chronic and persistent infection in the experimental murine model of tuberculosis induced aerogenically by a low-dose inoculum was determined in eight isoniazid-resistant clinical strains of Mycobacterium tuberculosis showing different catalase-peroxidase (C-P) activities. Determination of bacillary concentration in lung and spleen and the percentage of pulmonary parenchyma occupied by granulomas were monitored. Data showed no relation between the lack of C-P activity and the ability to develop a persistent infection, highlighting the potential of C-P negative strains to spread through the community.

Widespread bronchogenic dissemination makes DBA/2 mice more susceptible than C57BL/6 mice to experimental aerosol infection with Mycobacterium tuberculosis.

We have used the murine model of aerosol-induced experimental tuberculosis to assess the effects of four clinical isolates and a reference strain of Mycobacterium tuberculosis on resistant C57BL/6 mice and susceptible DBA/2 mice. Histological studies and detection of 25 cytokines potentially involved in the infection were carried out. DBA/2 mice showed higher concentrations of bacilli in bronchoalveolar lavage fluid and lung tissue.