Endogenous Il10 alleviates the systemic antiviral cellular immune response and T cell-mediated immunopathology in select organs of acutely LCMV-infected mice.
The immunoregulatory cytokine IL-10 suppresses T-cell immunity. The complementary question, whether IL-10 is also involved in limiting the collateral damage of vigorous T cell responses, has not been addressed in detail. Here, we report that the particularly strong virus-specific immune response during acute primary infection with the lymphocytic choriomeningitis virus (LCMV) in mice is significantly further increased in Il10-deficient mice, particularly regarding frequencies and cytotoxic activity of CD8(+) T cells. This increase results in exacerbating immunopathology in select organs, ranging from transient local swelling to an increased risk for mortality. Remarkably, LCMV-induced, T cell-mediated hepatitis is not affected by endogenous Il10. The alleviating effect of Il10 on LCMV-induced immunopathology was found to be operative in delayed-type hypersensitivity footpad-swelling reaction and in debilitating meningitis in mice of both the C57BL/6 and BALB/c strains. These strains are prototypic counterpoles for genetically imprinted type 1-biased versus type 2-biased T cell-mediated immune responses against various infectious pathogens. However, during acute LCMV infection, neither systemic cytokine patterns nor the impact of Il10 on LCMV-induced immunopathology differed conspicuously between these two strains of mice. This study documents a physiological role of Il10 in the regulation of a balanced T-cell response limiting immunopathological damage.
Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
Kristin
K
Jakobshagen
Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
Beate
B
Ward
Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
Nikola
N
Baschuk
Institute of Pathology, University Hospital Cologne, Cologne, Germany.
Sebastian
S
Huss
Department of Neuropathology, University Hospital Cologne, Cologne, Germany.
Anna
A
Brunn
Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
Monika
M
Malecki
Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
Michael
M
Fiolka
Department of Internal Medicine I, University Hospital Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
Gunther
G
Rappl
Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
Diana
D
Corogeanu
Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.
Ulrike
U
Karow
Institute of Medical Statistics, Informatics and Epidemiology, University Hospital Cologne, Cologne, Germany.
Petra
P
Schiller
Department of Internal Medicine I, University Hospital Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
Hinrich
H
Abken
Institute of Pathology, University Hospital Cologne, Cologne, Germany.
Lukas C
LC
Heukamp
Department of Neuropathology, University Hospital Cologne, Cologne, Germany.
Martina
M
Deckert
Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany; German Center for Infection Research (DZIF), partner site Bonn-Cologne, Cologne, Germany.
Martin
M
Krönke
Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany. Electronic address: olaf.utermoehlen@uk-koeln.de.
Olaf
O
Utermöhlen
D000818:Animals; D000998:Antiviral Agents / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005260:Female; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000503:physiopathology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D000998:Antiviral Agents; D016207:Cytokines; C556062:IL10 protein, mouse; D016753:Interleukin-10