無菌マウスの実験結核症

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A review was made on studies of tuberculosis using germfree animals appeared in the literature including the present authors. Miyakawa was the first who studied experimental tuberculosis in germfree animals, and described a lesser degree of abscess formation following subcutaneous infection, and smaller number of granulomas following intravenous infection in germfree guinea pigs in comparison with those in conventional ones. On the contrary, Suter and Kirsanow, and Huempfner and Deuschle reported no marked difference between germfree and conventional *mice on the viable bacterial unit in organs or lesions produced following infection with BCG or laboratory maintained H37Rv strain. Hobby et al reported that germfree mice showed more uniform sensitivity than conventional mice to infection with virulent tubercle bacilli, and further that the immunizing effect of BCG was revealed more efficiently in germfree than conventional mice. We compared the fate of organisms in organs and lesions produced in germfree (GF, axenic CD-1 and ICR-GF) and conventional mice (SPF, reared in SPF barrier or in vinyl isolators) following intravenous. infection with virulent bovine type tubercle bacilli strain Ravenel. The results revealed a remarkable difference between GF and SPF mice in later stages of infection, i.e., at 3 weeks in the large infection dose (106 viable unit level) and at 4 weeks and later in the small infecting dose (104 viable unit level). A greater propagation of organisms was found in the organs of GE mice than those of SPF mice with both large and small infection doses. A lesion produced in GF mice with the large dose was characterized by exudative and necrotic changes in the lung, kidney and heart, and lesser developed granulomas in the liver and spleen, while productive changes appeared in all the organs of SPF mice. A lesion in GF mice following small infection dose showed more progressive and extensive proliferation than that in SPF mice, , and was characterized by many histiocytes engorged with acid fast bacilli alike in Yersin type tuberculosis. By summing up the findings, it was considered that GF mice responded to phagocytosed bacteria with a reaction of the reticuloendothelial system and formed granulomas as seen in SPF mice, however, an inhibitory activity of phagocytic mononuclear cells in GF mice to the multiplication of intracellular mycobacteria seemed to be less comparing with that of SPF mice. Consequently, GF mice showed a higher bacterial unit in the organs and more extensive lesions than SPF mice later than 4 weeks, after infection. The above described characteristics of tuberculous infection of germfree mice led the authors to the studies on delayed type hypersensitivity (DTH) reaction in germfree mice. DTH represented by footpad reaction with PPD on infected GF mice showed very poor reaction 2e-d3 weeks after infection. During the same period, SPF mice responded markedly. Immunization of mice with a mycobacterial component (phenol extract residue) suspended in paraffin also showed an impaired DTH reaction in GF mice while a typical DTH reaction appeared in SPE mice. Depressed DTH reaction in GF animals was also reported by Lerner, and Lev and Battisto in guinea pigs. This impaired DTH reaction in GF mice seems to be related to, if not all the cause of, the low resistance of germfree mice to tuberculous infection.
日本結核病学会の論文

無菌マウスの実験結核症

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