Chronic Listeria infection in SCID mice: requirements for the carrier state and the dual role of T cells in transferring protection or suppression.
Listeriosis in mice with the SCID mutation results in a chronic infection. The chronic infection is characterized by abundant granulomas and neutrophil infiltrates. Both lesions were particularly noticeable in the liver. In the liver, about 95% are granulomas with 5% microabscesses involving intrahepatic infection. The majority of Listeria resided in membrane-bound vacuolar structures of the macrophages and not in the cytosol. Three manipulations resulted in alterations in the equilibrium between granulomas and liver microabscesses, with massive transfer of the infection to the hepatocyte and dissolution of the granulomas: depletion of neutrophils and neutralization of IFN-gamma and TNF-alpha. We did not find a role for IL-12, IL-10, or nitric oxide. Adoptive transfer studies showed a decisive role for both CD4+ and CD8+ T cells for an effective immune response, i.e., clearance of bacteria, granuloma formation with lymphocytes, and disappearance of microabscess. Clearance of Listeria was induced by transfer of CD8+ T cells from mice with targeted disruption of the IFN-gamma structural gene (IfgTM1KO), even in the presence of neutralizing mAb to IFN-gamma. In marked contrast, transfer of CD4+ T cells from IfgTM1KO mice exacerbated the infection in the chronically infected SCID mice, resulting in increased mortality with dissolution of the granulomas and severe hepatic infection with neutrophil infiltration. Thus, these data indicate that both IFN-gamma-dependent and -independent mechanisms are operative in the context of a chronic listerial infection.
Bhardwaj
V
V
Center for Immunology and Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Kanagawa
O
O
Swanson
P E
PE
Unanue
E R
ER
D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D016867:Immunocompromised Host; D007371:Interferon-gamma / Q000502:physiology; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma