Differences in gamma interferon production induced by listeriolysin O and ivanolysin O result in different levels of protective immunity in mice infected with Listeria monocytogenes and Listeria ivanovii.
Two pathogenic species in the genus Listeria, Listeria monocytogenes and Listeria ivanovii, are characterized by the production of hemolysins belonging to cholesterol-dependent cytolysins, listeriolysin O (LLO) and ivanolysin O (ILO), respectively. LLO, produced by L. monocytogenes, is able to induce gamma interferon (IFN-gamma) production and contributes to the generation of Th1-dependent protective immunity. On the other hand, nothing is known about the role of ILO, produced by L. ivanovii, in this regard. In this study, we immunized mice with 0.1 50% lethal dose (LD(50)) of L. monocytogenes and L. ivanovii. Protective immunity against a challenge with 10 LD(50) was generated in mice infected with L. monocytogenes, whereas L. ivanovii infection did not induce protection. After immunization, the level of IFN-gamma in serum samples was increased in mice given L. monocytogenes but not in those given L. ivanovii. To determine the IFN-gamma-inducing activity of cytolysins, recombinant protein was constructed. Recombinant ILO exhibited significantly lower IFN-gamma-inducing activity than LLO. By comparing the IFN-gamma-inducing activity of a chimera incorporating LLO and ILO, it was found that domains 1 to 3 of LLO were critical for IFN-gamma-inducing activity while the counterpart in ILO was unable to induce cytokine production. These results suggested that the weak ability of ILO to induce IFN-gamma production is responsible for the failure of L. ivanovii to generate effective protective immunity.
Kimoto
Terumi
T
Department of Microbiology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
Kawamura
Ikuo
I
Kohda
Chikara
C
Nomura
Takamasa
T
Tsuchiya
Kohsuke
K
Ito
Yutaka
Y
Watanabe
Isao
I
Kaku
Taijin
T
Setianingrum
Endang
E
Mitsuyama
Masao
M
D000595:Amino Acid Sequence; D000818:Animals; D001427:Bacterial Toxins; D005260:Female; D006360:Heat-Shock Proteins / Q000502:physiology*; D006460:Hemolysin Proteins; D007371:Interferon-gamma / Q000096:biosynthesis*; D008087:Listeria / Q000254:growth & development / Q000276:immunology*; D008089:Listeria monocytogenes / Q000254:growth & development / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data
D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D007371:Interferon-gamma; C038705:hlyA protein, Listeria monocytogenes