UNIGE document Scientific Article
previous document  unige:20730  next document
add to browser collection

Limited role for lymphotoxin alpha in the host immune response to Mycobacterium tuberculosis

Allie, Nasiema
Keeton, Roanne
Court, Nathalie
Abel, Brian
Fick, Lizette
Vasseur, Virginie
Vacher, Rachel
show hidden authors show all authors [1 - 15]
Published in Journal of Immunology. 2010, vol. 185, no. 7, p. 4292-4301
Abstract The contribution of lymphotoxin (LT)alpha in the host immune response to virulent Mycobacterium tuberculosis and Mycobacterium bovis bacillus Calmette-Guerin infections was investigated. Despite their ability to induce Th1 cytokine, IFN-gamma, and IL-12 pulmonary response, "conventional" LTalpha(-/-) 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 LTalpha(-/-) mice were excluded because hematopoietic reconstitution with conventional LTalpha(-/-) bone marrow conferred enhanced susceptibility to wild-type mice, comparable to conventional LTalpha(-/-) control mice. However, conventional LTalpha(-/-) mice produced reduced levels of TNF after M. bovis bacillus Calmette-Guerin infection, and their lack of control of mycobacterial infection could be due to a defective contribution of either LTalpha or TNF, or both, to the host immune response. To address this point, the response of "neo-free" LTalpha(-/-) mice with unperturbed intrinsic TNF expression to M. tuberculosis infection was investigated in a direct comparative study with conventional LTalpha(-/-) mice. Strikingly, although conventional LTalpha(-/-) mice were highly sensitive, similar to TNF(-/-) mice, neo-free LTalpha(-/-) mice controlled acute M. tuberculosis infection essentially as wild-type mice. Pulmonary bacterial burden and inflammation was, however, slightly increased in neo-free LTalpha(-/-) mice 4-5 mo postinfection, but importantly, they did not succumb to infection. Our findings revise the notion that LTalpha might have a critical role in host defense to acute mycobacterial infection, independent of TNF, but suggest a contribution of LTalpha in the control of chronic M. tuberculosis infection.
Keywords AnimalsCytokines/biosynthesis/immunologyEnzyme-Linked Immunosorbent AssayLymphotoxin-alpha/*immunology/metabolismMiceMice, Inbred C57BLMice, KnockoutMycobacterium bovis/immunologyMycobacterium tuberculosis/immunologyNitric Oxide Synthase Type II/biosynthesis/immunologyTuberculosis/*immunology/metabolismTumor Necrosis Factor-alpha/biosynthesis/immunology
PMID: 20817877
Full text
Research group Rôles des cytokines de la famille du TNF dans les infections mycobactériennes (500)
(ISO format)
ALLIE, Nasiema et al. Limited role for lymphotoxin alpha in the host immune response to Mycobacterium tuberculosis. In: Journal of Immunology, 2010, vol. 185, n° 7, p. 4292-4301. doi: 10.4049/jimmunol.1000650 https://archive-ouverte.unige.ch/unige:20730

397 hits

0 download


Deposited on : 2012-05-23

Export document
Format :
Citation style :