Membrane tumor necrosis factor confers partial protection to Listeria infection.
Tumor necrosis factor (TNF) plays a critical role in the host response to the intracellular pathogen Listeria monocytogenes (LM). TNF exists in soluble and membrane-bound forms and exhibits both unique and overlapping activities. We examined the role of membrane TNF in the absence of secreted TNF for host resistance in knockin mice in which the endogenous TNF was replaced by a regulated, noncleavable allele (mem-TNF). Macrophages expressing mem-TNF produced nitric oxide and displayed normal bactericidal activity. Although mice completely deficient in TNF (TNF(-/-)) succumbed to LM infection within 4 days, mem-TNF mice controlled LM infection at a low dose (10(4) CFU) but succumbed at a higher dose of infection (10(5) CFU). In contrast to complete TNF deficiency, mem-TNF mice developed confined microabscesses that expressed inducible nitric oxide synthase. The transfer of lymphocytes from immunized mem-TNF, but not TNF(-/-), mice protected TNF(-/-) mice from fatal infection. Taken together the data suggest that in the absence of soluble TNF, the presence of membrane-expressed TNF on phagocytes and lymphocytes partially restores host defense to LM infection.
Torres
David
D
Transgenose Institute, Centre National de la Recherche Scientifique, Molecular Immunology and Embryology, Orléans, France.
Janot
Laure
L
Quesniaux
Valerie F J
VF
Grivennikov
Sergei I
SI
Maillet
Isabelle
I
Sedgwick
Jonathon D
JD
Ryffel
Bernhard
B
Erard
Francois
F
D000818:Animals; D002462:Cell Membrane / Q000382:microbiology / Q000502:physiology*; D008089:Listeria monocytogenes / Q000472:pathogenicity*; D008088:Listeriosis / Q000517:prevention & control*; D008214:Lymphocytes / Q000382:microbiology / Q000502:physiology; D008264:Macrophages / Q000382:microbiology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000502:physiology; D010586:Phagocytes / Q000382:microbiology / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide