A mouse model for slowly progressive primary tuberculosis

Citation
T. Mustafa et al., A mouse model for slowly progressive primary tuberculosis, SC J IMMUN, 50(2), 1999, pp. 127-136
Citations number
40
Categorie Soggetti
Immunology
Journal title
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
ISSN journal
03009475 → ACNP
Volume
50
Issue
2
Year of publication
1999
Pages
127 - 136
Database
ISI
SICI code
0300-9475(199908)50:2<127:AMMFSP>2.0.ZU;2-4
Abstract
The progression from primary Mycobacterium tuberculosis infection to diseas e is usually slow in humans. The aim of this study was to develop and chara cterize a mouse model for slowly progressive primary tuberculosis, using th e intraperitoneal (i.p.) route of infection, and to compare it with our pre viously described model of latent M, tuberculosis infection. B6D2F1 hybrid mice inoculated with 1.5 x 10(6) colony-forming units (CFUs) of M, tubercul osis H37Rv were followed-up for 70 weeks. Lungs, livers and spleens were ex amined for bacillary growth, histopathological changes and mycobacterial an tigens (MPT64, ManLAM and multiple antigens of M. tuberculosis), by immunoh istochemical staining. The infection was found to pass through three distin ctive phases. During phase 1, mice were healthy despite development of smal l granulomas and an increasing number of bacilli in the lungs. During phase 2, mice were unwell but mortality was low. The count of M, tuberculosis an d the granuloma size stabilized. The granulomas contained an increasing pop ulation of large, vacuolated macrophages. During phase 3, mice became morib und and died rapidly, but the M. tuberculosis count remained relatively sta ble. The inflammatory infiltrates filled approximate to 80% of the lung par enchyma and the lesions were not well demarcated. Rapidly progressing infla mmation, rather than an increase in the M. tuberculosis count, seems to con tribute more to mortality.