Mycobacterium intracellulare感染症モデル動物としての免疫不全マウスおよび同ラット

抄録

In order to establish an animal model for disseminated M. avium complex (MAC) infections frequently encountered in AIDS patients, we studied growth of M. intracellulare in visceral organs (lungs, livers, spleens, kidneys), in blood, and in footpads of mice with defined immunodeficiencies, such as SCID mice with T and B cell-defect, BALB/c athymic nude mice with matured T cell-defect, and beige mice with NK cell-defect. In addition, Sprague-Dawley rats with acquired immunodeficiency induced by cyclosporine-treatment were also examined. The following results were obtained.
1) SCID mice: First, SCID mice were infected sc with 6.1×10⁶ CFU of M. intracellulare N-260 (virulent SmT colonial variant) into the hind footpad. The organisms grew in the footpad remarkably during the 12 weeks after infection in SCID mice, where the growth rate was much greater than that in CB-17 strain mice with the same genotype as SCID mice and in BALB/c mice with Beg^s genotype (CB-17 and BALB/c mice are MAC-susceptible). Furthermore, in SCID mice, bacteremia and dissemination of organisms to the visceral organs were observed but not in the two control strains of mice.
Second, SCID mice were infected iv with 4.8×10⁶ CFU. The bacterial loads in the viscera of SCID mice after infection were larger than those of CB-17 mice except for livers. However, the incidence and the degree of gross lung lesions were much less in SCID mice compared to CB-17 mice, presumably due to the defect in T cell-mediated immune reactions in SCID mice.
2) BALB/c athymic nude mice and beige mice: Various strains of mice (BALB/c athymic nude, beige, SCID, CB-17, BALB/c euthymic) were infected iv with 4.8×10⁶ CFU of M. intracellulare N-260. The severity of the pulmonary lesions and the size of bacterial loads in the lungs were the greatest in beige mice. On the other hand, the bacterial loads in the spleens and kidneys of SCID mice and BALB/c athymic nude mice were similar and higher when compared to those in beige, CB-17, and BALB/c mice.
3) Cyclosporine-treated Sprague-Dawley rats: In the cyclosporine-treated rats, ivinfection with 2.1×10⁷ CFU of M. intracellulare N-260 resulted in a slight increase in the bacterial loads in the lungs and spleens during the first 8 weeks after infection. This suggests that persistent infection was inducible in the cyclosporine-treated rats. In contrast, organisms were gradually eliminated from lungs and spleens in normal rats.
These findings indicate that a systemic infection can be induced by challenging M. intracellulare into the footpad of SCID mice. This experimental system may serve as a model for the disseminated MAC infections seen in immune compromised hosts such as AIDS patients.