The Relation between the Host Susceptibility and the Disease Type in Mouse Leprosy

Abstract

For the purpose of selecting an adequate experimental strain, comparative observations were made of the susceptibility of various inbred mouse strains (C57BL/6, dba, NC, A, A # 1, ddD, ddY, CFW, CF # 1, SM, BALB/C, C3H/He and C3H) to subcutaneous infection with murine leprosy bacilli under the same dietary and environmental conditions. Significant differences in the susceptibility were revealed among these strains, C57BL/6 and C3H being the most characteristic ones with a striking contrast.
With further progress of the studies on the clinical features of skin lesions and the disease courses, the author was led to a consideration that mouse leprosy should be classified into two polar types, benign and malignant. In the former type which is represented by C57BL/6 strain, the leproma appears early and is small, hard and sharply defined, whereas the leproma of the latter type which is represented by C3H strain develops slower but is much larger and soft with a diffuse thickening appearance. In the malignant type, infection is in general progressive, with fatal termination. In the benign type, however, the disease may undergo gradual regression and sometimes resulted in spontaneous healing in the late stage.
The development of visceral lesions was examined in these two types after subcutaneous inoculation. In the early stage of infection, visceral lesions of both types were so slight that a few murine lepra cells could be found in a smear prepared from the visceral organs. In the late stage, however, significant differences were evident between these two types. The visceral lesions of benign cases remained slight, whereas those of the malignant cases became severer with time to such an extent as comparable to the cases of intraperitoneal infection.
The remarkable differences in response to subcutaneous infection such as above led us to a further attempt to examine whether the similar situation might be present also in the case of intraperitoneal infection. However, no significant difference was observed concerning the mode of infection between the two strains, C57BL/6 and C3H. Even in the mice of C57BL/6 strain, visceral lesions became worse in the course of time. In the later stage of infection, the spleen and liver were enormously enlarged with color change to white, and numerous murine lepra cells were found in smears from the organs. Moreover, similar results were obtained in the cases of C3H strain. In view of these findings, our discussion of the disease type of mouse leprosy should be confined within the case of subcutaneous infection
Meanwhile, in the course of our study on the usefulness of the first generation hybrids in experimental mouse leprosy, it was found that hybrids obtained by crossing females of the intermediate strain, such as CF# 1 or dd, with males of the susceptible strain, such as C57BL/6 or C3H, showed similar properties to their fathers. The susceptibility of hybrids from reciprocal crosses between the two polar strains, C57BL/6 and C3H, was examined. Most of the hybrids showed the intermediate characters and they lost the characters of their parental strains. Taking these facts into consideration, the manifestation of the features of skin lesions is undoubtedly due to hereditary disposition.
The nature of infectious immunity was investigated on the two disease types, with reference to the variation in susceptibility to murine leprosy. The experimental animals were infected subcutaneously with murine leprosy bacilli in the abdomen and then subjected to subcutaneous superinfection in the breast at varying intervals. In response to the challenge at the time when primary lesions were still unpalpable, the mice of the benign type showed only a slight difference, in the size of leproma due to challenge infection, from the control mice without primary infection. However, when superinfection was made after primary lesions had fully been established,