LIGHT contributes to early but not late control of Mycobacterium tuberculosis infection.
The TNF superfamily member, LIGHT, contributes to optimal T-cell activation in vitro through co-stimulation of dendritic cell cytokine production; however, its role in T-cell-mediated control of intracellular bacterial infections is unknown. Protective immunity against Listeria monocytogenes and Mycobacterium tuberculosis infection requires both antigen-specific CD4(+) and CD8(+) T cells. Using LIGHT-deficient mice we determined that LIGHT was necessary for optimal re-stimulation of anti-listerial CD8(+) T cells in vitro. By contrast, LIGHT(-/-) mice infected with L. monocytogenes generated equivalent T-cell responses and controlled the infection as effectively as normal C57BL/6 mice. Following M. tuberculosis infection, LIGHT(-/-) mice showed a significant increase in bacterial replication in the lungs at 4 weeks, but by 6 weeks had controlled the infection. Analysis of T-cell responses in vivo revealed that LIGHT was dispensable for the activation of primary T-cell responses and the production of IL-12 and IFN-gamma. In addition, LIGHT was not required for the induction of memory T-cell responses to anti-mycobacterial DNA or BCG vaccines and for subsequent protection against tuberculosis challenge. Therefore, LIGHT contributes to the optimal co-stimulation of anti-listerial CD8(+) T-cell responses in vitro and to the early control of M. tuberculosis infection; however, other mechanisms compensate for LIGHT deficiency in the control of these pathogens in vivo.
Musicki
Korana
K
Mycobacterial Research Program, Centenary Institute, Locked Bag No. 6, Newtown, New South Wales 2042, Australia.
Briscoe
Helen
H
Britton
Warwick J
WJ
Saunders
Bernadette M
BM
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation; D008089:Listeria monocytogenes / Q000276:immunology / Q000302:isolation & purification; D051379:Mice; D008810:Mice, Inbred C57BL; D009164:Mycobacterium Infections / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000302:isolation & purification; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000172:deficiency / Q000276:immunology*
D053326:Tumor Necrosis Factor Ligand Superfamily Member 14