Immunological basis of the development of necrotic lesions following Mycobacterium avium infection

• Type: Article in International Scientific Journal
• Date: 2002

Authors

Florido, M (Author) Other; Cooper, AM (Author) Other; Appelberg, R (Author) ICBAS

Journal

Title: Immunology

Vol. 106

Pages: 590-601

ISSN: 0019-2805

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 40 Citations

Scopus - 39 Citations

Pubmed / Medline

Scientific classification

FOS: Medical and Health sciences > Basic medicine

CORDIS: Health sciences > Medical sciences > Medicine > Infections

Other information

Authenticus ID: P-000-NFZ

DOI: 10.1046/j.1365-2567.2002.01459.x

Abstract (EN): Normal C57BL/6 mice infected with 10(6) colony-forming units of a highly virulent strain of Mycobacterium avium developed a progressive infection characterized by loss of T cells from the tissues and infiltration with high numbers of heavily infected macrophages. In contrast, when C57BL/6 mice were infected with 10(2) colony-forming units of the same strain they retained T cells and T-cell reactivity in the tissues, and granulomas evolved into large masses that, at 4 months of infection, exhibited central necrosis. The development of these necrotic lesions did not occur in nude mice, nor in mice genetically deficient in CD4, interleukin-12 (IL-12) p40, interferon-gamma (IFN-gamma) and CD40 and were reduced in mice deficient in CD54 or IL-6. They were less numerous but bigger in mice deficient in IL-10 or the inducible nitric oxide synthase, correlating with the increased resistance to mycobacterial proliferation of these strains as compared to control mice. The appearance of necrosis was not affected in mice deficient in CD8alpha, T-cell receptor delta, tumour necrosis factor receptor p55, and perforin, nor was it affected in mice over-expressing bcl2. The appearance of necrosis could be prevented by administering antibodies specific for CD4, IL-12p40, or IFN-gamma from the second month of infection when organized granulomas were already found. Our results show that the immunological mediators involved in the induction of protective immunity are also major players in the immunopathology associated with mycobacteriosis.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12