Affiliation:
1. Experimental Pathology Section, Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición ‘Salvador Zubirán’, Mexico City, México
2. Department of Medical Microbiology, Windeyer Institute of Medical Sciences, Royal Free and University College Medical School, London, UK
Abstract
SUMMARY
Mycobacterium tuberculosis produces latent infection or progressive disease. Indeed, latent infection is more common since it occurs in one-third of the world's population. We showed previously, using human material with latent tuberculosis, that mycobacterial DNA can be detected by in situ PCR in a variety of cell types in histologically-normal lung. We therefore sought to establish an experimental model in which this phenomenon could be studied in detail. We report here the establishment of such a model in C57Bl/6 × DBA/2 F1 hybrid mice by the intratracheal injection of low numbers of virulent mycobacteria (4000). Latent infection was characterized by low and stable bacillary counts without death of animals. Histological and immunological study showed granulomas and small patches of alveolitis, with high expression of tumour necrosis factor alpha (TNFα), inducible nitiric oxide synthase (iNOS), interleukin 2 (IL-2) and interferon gamma (IFNγ). In contrast, the intratracheal instillation of high numbers of bacteria (1 × 106) produced progressive disease. These animals started to die after 2 months of infection, with very high bacillary loads, massive pneumonia, falling expression of TNF-α and iNOS, and a mixed Th1/Th2 cytokine pattern. In situ PCR to detect mycobacterial DNA revealed that the most common positive cells in latently-infected mice were alveolar and interstitial macrophages located in tuberculous lesions, but, as in latently-infected human lung, positive signals were also seen in bronchial epithelium, endothelial cells and fibroblasts from histologically-normal areas. Our results suggest that latent tuberculosis is induced and maintained by a type 1 cytokine pattern plus TNFα, and that mycobacteria persist intracellularly in lung tissue with and without histological evidence of a local immune response.
Publisher
Oxford University Press (OUP)
Subject
Immunology,Immunology and Allergy
Reference32 articles.
1. Mechanisms of latency in Mycobacterium tuberculosis;Parrish;Trends Microbiol,1998
2. Tuberculosis: a global overview of the situation today;Sudre;Bull WHO,1992
3. The global tuberculosis situation and the new control strategy of the World Health Organization;Kochi;Tubercle,1991
4. Dormancy of Mycobacterium tuberculosis and latency of disease;Wayne;Eur J Clin Microbiol Infect Dis,1994
5. Global tuberculosis incidence and mortality during 1990–2000;Dolin;Bull WHO,1994
Cited by
81 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献