Highly biased type 1 immune responses in mice deficient in LFA-1 in Listeria monocytogenes infection are caused by elevated IL-12 production by granulocytes.
LFA-1 (CD11a/CD18) plays a key role in various inflammatory responses. Here we show that the acquired immune response to Listeria monocytogenes is highly biased toward type 1 in the absence of LFA-1. At the early stage of listeriosis, numbers of IFN-gamma producers in the liver and spleen of LFA-1(-/-) mice were markedly increased compared with heterozygous littermates and Valpha14(+)NKT cell-deficient mice, and NK cells were major IFN-gamma producers. Numbers of IL-12 producers were also markedly elevated in LFA-1(-/-) mice compared with heterozygous littermates, and endogenous IL-12 neutralization impaired IFN-gamma production by NK cells. Granulocyte depletion diminished numbers of IL-12 producers and IFN-gamma-secreting NK cells in the liver of LFA-1(-/-) mice. Granulocytes from the liver of L. monocytogenes-infected LFA-1(-/-) mice were potent IL-12 producers. Thus, in the absence of LFA-1, granulocytes are a major source of IL-12 at the early stage of listeriosis. We assume that highly biased type 1 immune responses in LFA-1(-/-) mice are caused by increased levels of IL-12 from granulocytes and that granulocytes play a major role in IFN-gamma secretion by NK cells. In conclusion, LFA-1 regulates type 1 immune responses by controlling prompt infiltration of IL-12-producing granulocytes into sites of inflammation.
Emoto
Masashi
M
Department of Immunology, Max-Planck- Institute for Infection Biology, Berlin, Germany. emoto@mpiib-berlin.mpg.de
Miyamoto
Mamiko
M
Emoto
Yoshiko
Y
Yoshizawa
Izumi
I
Brinkmann
Volker
V
van Rooijen
Nico
N
Kaufmann
Stefan H E
SH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D006098:Granulocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007110:Immunity, Active / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1; D018664:Interleukin-12; D007371:Interferon-gamma