Listeriosis in p47(phox-/-) and TRp55-/- mice: protection despite absence of ROI and susceptibility despite presence of RNI.
The significance of host defense mechanisms in primary listeriosis in vivo is incompletely understood. Here, we show that tumor necrosis factor receptor p55-/- (TRp55-/-) mice are susceptible to Listeria monocytogenes infection in the presence of leukocyte recruitment, inflammatory cytokine production (including IFNgamma), nitric oxide synthesis, and oxidative burst formation. Mice deficient for oxidative burst (p47[phox-/-] mice) are relatively resistant to listeriosis. Despite activation of these antibacterial effector systems, TRp55-/- phagocytes in vivo are incapable of confining and eradicating L. monocytogenes inside phagolysosomes. Bone marrow chimeras reveal that for eradication of L. monocytogenes, TRp55 is crucially required only on cells from hematopoietic origin. Unexpectedly, prior to death, exocrine pancreatic cells undergo apoptosis in TRp55-/- mice. Collectively, these data demonstrate that in vivo, TRp55 initiates a protective, listericidal mechanism in phagocytes that differs from nitric oxide production and oxidative burst formation and that uncontrolled listeriosis results in necrotizing pancreatitis in TRp55-/- mice.
Endres
R
R
Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Federal Republic of Germany.
Luz
A
A
Schulze
H
H
Neubauer
H
H
Fütterer
A
A
Holland
S M
SM
Wagner
H
H
Pfeffer
K
K
D000818:Animals; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D001853:Bone Marrow / Q000502:physiology; D002678:Chimera; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004198:Disease Susceptibility; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology; D010586:Phagocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D010750:Phosphoproteins / Q000276:immunology* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology* / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D016897:Respiratory Burst / Q000276:immunology*; D015854:Up-Regulation
D015703:Antigens, CD; D016207:Cytokines; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D009584:Nitrogen