In:
The Journal of Immunology, The American Association of Immunologists, Vol. 185, No. 7 ( 2010-10-01), p. 4292-4301
Abstract:
The contribution of lymphotoxin (LT)α in the host immune response to virulent Mycobacterium tuberculosis and Mycobacterium bovis bacillus Calmette-Guérin infections was investigated. Despite their ability to induce Th1 cytokine, IFN-γ, and IL-12 pulmonary response, “conventional” LTα−/− mice succumb rapidly to virulent M. tuberculosis aerosol infection, with uncontrolled bacilli growth, defective granuloma formation, necrosis, and reduced pulmonary inducible NO synthase expression, similar to TNF−/− mice. Contributions from developmental lymphoid abnormalities in LTα−/− mice were excluded because hematopoietic reconstitution with conventional LTα−/− bone marrow conferred enhanced susceptibility to wild-type mice, comparable to conventional LTα−/− control mice. However, conventional LTα−/− mice produced reduced levels of TNF after M. bovis bacillus Calmette-Guérin infection, and their lack of control of mycobacterial infection could be due to a defective contribution of either LTα or TNF, or both, to the host immune response. To address this point, the response of “neo-free” LTα−/− mice with unperturbed intrinsic TNF expression to M. tuberculosis infection was investigated in a direct comparative study with conventional LTα−/− mice. Strikingly, although conventional LTα−/− mice were highly sensitive, similar to TNF−/− mice, neo-free LTα−/− mice controlled acute M. tuberculosis infection essentially as wild-type mice. Pulmonary bacterial burden and inflammation was, however, slightly increased in neo-free LTα−/− mice 4–5 mo postinfection, but importantly, they did not succumb to infection. Our findings revise the notion that LTα might have a critical role in host defense to acute mycobacterial infection, independent of TNF, but suggest a contribution of LTα in the control of chronic M. tuberculosis infection.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.1000650
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2010
detail.hit.zdb_id:
1475085-5
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