Expression of an adenovirally encoded lymphotoxin-beta inhibitor prevents clearance of Listeria monocytogenes in mice.
The lymphotoxin (LT)-beta heterotrimer was recently identified as a molecule containing LT-alpha subunits, tethered to the cell through non-covalent association with an integral plasma membrane protein, derived from the LT-beta gene. Since knockout mutations of the LT-alpha gene yield animals that lack lymph nodes, whereas animals lacking either or both of the receptors for tumor necrosis factor (TNF) and LT-alpha homotrimers have normal lymph nodes, it has been inferred that the association between the LT-beta heterotrimer and its cognate receptor is required for lymph node ontogeny. Similarly, LT-beta and its receptor are thought to be important for development of the spleen. Since LT-alpha deficient mice lack lymph nodes, it is difficult to assess the extradevelopmental contribution of LT-beta to immune competence. To this end, we employed a strategy for the conditional blockade of LT-beta heteromer activity in normal mice. The interaction between LT-beta and its receptor is essential for the destruction of intracellular Listeria monocytogenes.
Trüeb
R
R
Department of Dermatology, Howard Hughes Medical Institute, Dallas, Texas, USA.
Brown
G
G
Van Huffel
C
C
Poltorak
A
A
Valdez-Silva
M
M
Beutler
B
B
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004198:Disease Susceptibility; D005821:Genetic Techniques; D005822:Genetic Vectors; D007107:Immune System / Q000502:physiology*; D008089:Listeria monocytogenes / Q000502:physiology*; D008088:Listeriosis / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*; D053308:Lymphotoxin-beta; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
C505887:Ltb protein, mouse; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha