Essential role of interleukin-12 (IL-12) and IL-18 for gamma interferon production induced by listeriolysin O in mouse spleen cells.
The mechanism of gamma interferon (IFN-gamma) production induced by listeriolysin O (LLO), a cytolytic virulence factor of Listeria monocytogenes, was analyzed with special reference to the involvement of macrophage-derived cytokines in spleen cells of mice. LLO purified from the culture supernatant of L. monocytogenes was capable of inducing a high level of IFN-gamma when its cytolytic activity was blocked by cholesterol treatment. The IFN-gamma-inducing ability of LLO was not dependent on possibly contaminating lipopolysaccharide. Depletion of CD11b(+) cells resulted in a profound decrease in IFN-gamma production in response to LLO stimulation. Negative selection also suggested the contribution of DX5(+) cells in IFN-gamma production. Reverse transcription-PCR revealed that expression of interleukin-12 (IL-12) p35 and p40 was induced by LLO but that the IL-18 mRNA level in the CD11b(+) fraction of spleen cells was unchanged. There was no change in the expression of the IFN-gamma-inducing cytokine genes in the CD11b(-) fraction. Neutralization of IL-12 and IL-18 in culture abolished the IFN-gamma production almost completely. Spleen cells from IL-12- or IL-18-deficient mice never produced IFN-gamma after stimulation with LLO. These results clearly indicated that LLO, a well-known virulence factor of L. monocytogenes, is capable of inducing IFN-gamma from NK cells through induction of IL-12 and IL-18 from macrophages. LLO appeared to play essential roles, not only as a bacterial virulence factor but also as a bacterial modulin in the immune response of the host.
Nomura
Takamasa
T
Department of Microbiology, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
Kawamura
Ikuo
I
Tsuchiya
Kohsuke
K
Kohda
Chikara
C
Baba
Hisashi
H
Ito
Yutaka
Y
Kimoto
Terumi
T
Watanabe
Isao
I
Mitsuyama
Masao
M
D000818:Animals; D001427:Bacterial Toxins; D005260:Female; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D006460:Hemolysin Proteins / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000172:deficiency / Q000378:metabolism*; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D020382:Interleukin-18 / Q000172:deficiency / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000472:pathogenicity; D016177:Macrophage-1 Antigen / Q000302:isolation & purification; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021122:Protein Subunits; D013154:Spleen / Q000166:cytology / Q000276:immunology*
D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D020382:Interleukin-18; D016177:Macrophage-1 Antigen; D021122:Protein Subunits; D018664:Interleukin-12; D007371:Interferon-gamma; C038705:hlyA protein, Listeria monocytogenes