Abstract
Recently, we reported that heat-killedLactobacillus casei (LC) protected mice from murine cytomegalovirus (MCMV) infection by augmentation of natural killer (NK) cell activity. In the present study, we examined which components of LC cell induce the nonspecific resistance most effectively. Whole cell preparation of original LC, susceptible to bacteriophages SG-T and J1, was more effective than its mutants resistant to either bacteriophage. Although the activity of LC cells decreased upon fractionation, cell wall fractions were more active than cytoplasmic fractions. Glycoprotein (GP), a cell wall constituent, was a potent inducer of the resistance. The relative activity of cellular components to induce the resistance was evaluated by a protection index, a ratio of plaque-forming units (PFU) per 50% lethal dose (LD50) for treated mice to that for untreated mice. The protection indices of LC cells and GP were approximately 80 and 28, respectively. The protective effect of GP was evidenced by a decrease in titers of infectious viruses replicated in the target organs. Not only LC cells but also GP, although to a lesser degree, enhanced NK cell activity both in uninfected mice and MCMV-infected mice. The activity of LC cells and GP to augment NK cell activity correlated with the protection index. GP treatment did not modify interferon (IFN) production during MCMV infection. Thus, GP of LC cells seems to be the active principle to endow mice with resistance to MCMV.
Similar content being viewed by others
References
Kato I, Kobayashi S, Yokokura T, Mutai M. Antitumor activity ofLactobacillus casei in mice. Gann 1981; 72: 517–23.
Yasutake N, Kato I, Ohwaki M, Yokokura T, Mutai M. Host-mediated antitumor activity ofLactobacillus casei in mice. Gann 1984; 75: 72–80.
Miake S, Nomoto K, Yokokura T, Yoshikai Y, Mutai M, Nomoto K. Protective effect ofLactobacillus casei onPseudomonas aeruginosa infection in mice. Infect Immun 1985; 48: 480–5.
Watanabe T, Saito H. Protection of mice against herpes simplex virus infection by aLactobacillus casei preparation (LC9018) in combination with inactivated viral antigen. Microbiol Immunol 1986; 30: 111–22.
Ohashi T, Yoshida A, Minamishima Y. Host-mediated antiviral activity ofLactobacillus casei against cytomegalovirus infection in mice. Biotherapy 1988; 1: 27–39.
Minamishima Y, Eizuru Y, Yoshida A, Fukunishi R. Murine model for immunophylaxis of cytomegalovirus infection: I Efficacy of immunization. Microbiol Immunol 1978; 22: 693–700.
Habu Y, Nagaoka M, Yokokura T, Azuma I. Structural studies of cell wall polysaccharides fromBifidobacterium breve YIT 4020 and relatedBifidobacterium species. J Biochem 1987; 102: 1423–32.
Yokokura T. Phage receptor material inLactobacillus casei. J Gen Microbiol 1977; 100: 139–45.
Ebihara K, Minamishima Y. Protective effect of biological modifiers on murine cytomegalovirus infection. J Virol 1984; 51: 117–22.
Bancroft GJ, Shellam GR, Chalmer JE. Genetic influences on the augmentation of natural killer (NK) cells during murine cytomegalovirus infection: Correlation with patterns of resistance. J Immunol 1981; 126: 988–94.
Shellam GR, Allan JE, Papadimisriou JM, Bancroft GJ. Increased susceptibility to cytomegalovirus infection in beige mutant mice. Proc Natl Acad Sci USA 1981; 78: 5104–8.
Bukowski JF, Woda BA, Welsh RM. Pathogenesis of murine cytomegalovirus infection in natural killer celldepleted mice. J Virol 1984; 52: 119–28.
Grundy (Chalmer) JE, Trapman J, Allan JE, Shellam GR, Melief CJM. Evidence for a protective role of interferon in resistance to murine cytomegalovirus and its control by non-H-2-linked genes. Infect Immun 1982; 37: 143–50.
Chong KT, Gresser I, Mims CA. Interferon as a defence mechanism in mouse cytomegalovirus infection. J Gen Virol 1983; 64: 461–4.
Kato K, Yamamoto K, Okuyama H, Kimura T. Microbicidal activity and morphological characteristics of lung macrophages inMycobacterium bovis BCG cell wallinduced lung granuloma in mice. Infect Immun 1984; 45: 325–31.
Kranhenbuhl JL, Sharma SD, Ferraresi RW, Remington JS. Effects of muramyl dipeptide treatment on resistance to infection withToxoplasma gondii in mice. Infect Immun 1981; 31: 716–22.
Osada Y, Mitsuyama M, Une T, Matsumoto K, Otani T, Satoh M, Ogawa H, Nomoto K. Effect of L18-MDP (Ala), a synthetic derivative of muramyl dipeptide, on nonspecific resistance of mice to microbial infections. Infect Immun 1982; 37: 292–300.
Galleli A, Garrec YL, Chedid L. Increased resistance and decreased delayed-type hypersensitivity toListeria monocytogenes induced by pretreatment with lipopolysaccharide. Infect Immun 1981; 31: 88–94.
Kato I, Yokokura T, Mutai M. Macrophage activation byLactobacillus casei in mice. Microbiol Immunol 1983; 27: 611–8.
Kato I, Yokokura T, Mutai M. Augmentation of mouse natural killer cell activity byLactobacillus casei and its surface antigens. Microbiol Immunol 1984; 28: 209–17.
Yokokura T, Nomoto K, Shimizu T, Nomoto K. Enhancement of hematopoietic response of mice by subcutaneous administration ofLactobacillus casei. Infect Immun 1986; 52: 156–60.
Tatsukawa K, Mitsuyama M, Takeya K, Nomoto K. Differing contribution of polymorphonuclear cells and macrophages to protection of mice againstListeria monocytogenes andPseudomonas aeruginosa. J Gen Microbiol 1979; 115: 161–6.
Griffith PD, Grundy JE. Molecular biology and immunology of cytomegalovirus. Biochem J 1987; 241: 313–24.
Ohashi T, Nawa Y, Minamishima Y, Owhashi M. Susceptibility of W/Wv mice to murine cytomegalovirus infection. Arch Virol 1988; 101: 237–246.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ohashi, T., Minamishima, Y., Yokokura, T. et al. Induction of resistance in mice against murine cytomegalovirus by cellular components ofLactobacillus casei . Biotherapy 1, 89–95 (1989). https://doi.org/10.1007/BF02170139
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02170139