Transient control of interleukin-4-producing natural killer T cells in the livers of Listeria monocytogenes-infected mice by interleukin-12.
Unconstrained development of gamma interferon (IFN-gamma)-secreting natural killer (NK) cells and T helper (Th) 1 cells is central to protection against Listeria monocytogenes. In contrast, interleukin 4 (IL-4) is considered harmful. IL-12 produced by infected macrophages promotes, and IL-4 interferes with, protective antilisterial immunity. The liver NK T lymphocytes, which are a potent source of IL-4, are downregulated at an intermediate stage of listeriosis. Here we demonstrate that endogenous IL-12 participates in the control of IL-4-producing liver NK T lymphocytes during listeriosis. The effects of L. monocytogenes infection on IL-4-producing liver NK T lymphocytes were reversed by antibody neutralization of IL-12 but not of IFN-gamma or tumor necrosis factor alpha (TNF-alpha). IL-4 production by liver NK T lymphocytes was virtually unaffected by heat-killed L. monocytogenes (HKL). Viable L. monocytogenes markedly increased the numbers of IL-12 producers in livers in parallel with an increase in macrophage numbers, whereas HKL failed to do so with similar efficiency. These results indicate that in the liver endogenous IL-12 improves protective immunity against listeriosis by downregulating IL-4-producing NK T lymphocytes. Moreover, our findings that HKL have a low level of IL-12-inducing activity and fail to control IL-4-producing NK T lymphocytes in the liver are consistent with the lesser protective capacity of HKL compared to that of live listeriae.
Emoto
Y
Y
Department of Immunology, University of Ulm, Germany.
Emoto
M
M
Kaufmann
S H
SH
D000818:Animals; D018664:Interleukin-12 / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D008099:Liver / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL
D018664:Interleukin-12; D015847:Interleukin-4