Interleukin-1 is responsible for acute lung immunopathology but increases survival of respiratory influenza virus infection.
Interleukin-1alpha (IL-1alpha) and IL-1beta are proinflammatory cytokines, which induce a plethora of genes and activities by binding to the type 1 IL-1 receptor (IL-1R1). We have investigated the role of IL-1 during pulmonary antiviral immune responses in IL-1R1(-/-) mice infected with influenza virus. IL-1R1(-/-) mice showed markedly reduced inflammatory pathology in the lung, primarily due to impaired neutrophil recruitment. Activation of CD4(+) T cells in secondary lymphoid organs and subsequent migration to the lung were impaired in the absence of IL-1R1. In contrast, activation of virus-specific cytotoxic T lymphocytes and killing of virus-infected cells in the lung were intact. Influenza virus-specific immunoglobulin G (IgG) and IgA antibody responses were intact, while the IgM response was markedly reduced in both serum and mucosal sites in IL-1R1(-/-) mice. We found significantly increased mortality in the absence of IL-1R1; however, lung viral titers were only moderately increased. Our results demonstrate that IL-1alpha/beta mediate acute pulmonary inflammatory pathology while enhancing survival during influenza virus infection. IL-1alpha/beta appear not to influence killing of virus-infected cells but to enhance IgM antibody responses and recruitment of CD4(+) T cells to the site of infection.
Schmitz
Nicole
N
Molecular Biomedicine, ETH Zurich, Wagistrasse 27, 8952 Zurich, Switzerland. Manfred.Kopf@ethz.ch
Kurrer
Michael
M
Bachmann
Martin F
MF
Kopf
Manfred
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D007111:Immunity, Cellular; D007249:Inflammation / Q000473:pathology; D007375:Interleukin-1 / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils; D009975:Orthomyxoviridae; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000172:deficiency / Q000235:genetics; D012141:Respiratory Tract Infections / Q000276:immunology*
D007375:Interleukin-1; D017472:Receptors, Interleukin-1