Suppression of babesiosis in BCG-infected mice and its correlation with tumor inhibition

Abstract

Infection of mice with Bacillus Calmette-Guerin (BCG) provided good protection against Babesia species. The intensity and duration of this protection was similar to that established after natural recovery from babesiosis. It developed too soon after the first exposure to the parasite, and was too radioresistant, to be attributable to specific antibody production. In addition, the parasites degenerated within circulating erythrocytes. This phenomenon is inconsistent with phagocytosis or lysis of parasites or parasitized cells, or prevention of entry of parasites into erythrocytes, causing the observed protection. Hence the phenomenon is best explained by the release of a nonspecific mediator that can limit multiplication of parasites within erythrocytes. These results not only throw light on mechanisms of immunity against hemoprotozoa. There are many points of similarity between the nonspecific protection BCG and Corynebacterium parvum provide against Babesia species and inhibition of tumor growth by these agents. Therefore, babesiosis in mice may be a convenient experimental model for assessing stimulation of the mononuclear phagocyte system, which appears to be the basis of nonspecific immunity against bacteria, parasites, and tumors.

Protection of mice against Babesia microti with cord factor, COAM, zymosan, glucan, Salmonella and Listeria

“…Clearly protection afforded by this diverse range of agents is most unlikely to be due to antigenic similarity causing a cross-reacting specific immune response. In view of our results with irradiation and CY described in this paper and elsewhere (Clark et al 1977b) protection is equally unlikely to be mediated by an enhanced specific antibody response. Another possibility is that this protozoan may be very susceptible to the poorly defined non-specific mechanism(s) by which these agents protect against certain other infections, agents and tumours.…”

“…As in mice protected against B. microti with BCG (Clark et al 1977b), C. paruum (Clark et al 1977a) or B. abortus S19 (Herod et al 1978) the inclusion bodies shown to be degenerate intra-erythrocytic parasites (Clark et al 1977c) were present in red cells of protected mice in these experiments. The dead parasites had the same appearance and were as common as those previously illustrated by light microscopy (Clark et al 1977a, 1977b, 1977c, Herod et al 1978) and electron microscopy (Clark et al 1977b. Again, parasites could not be detected in macrophages on impression smears from spleens and livers of protected mice.…”

“…In the present report, as with BCG-induced protection against B. microti (Clark et al 1977b), the failure of CY or irradiation to affect the course of protection, and intra-erythrocytic death of the parasites, imply that we must look beyond increased phagocytosis or production of specific antibody for an interpretation of these observations. Nevertheless intra-erythrocytic death of the parasites seems to be the work of some type of soluble mediator.…”

“…Mice pretreated with cord factor, COAM, zymosan, S. typhimurium or L. monocytogenes, and then demonstrated to be refractory to infection with B. microti, were still resistant to this parasite from 4 to 11 months later. We have shown, with BCG, that this occurs in the absence of recrudescence during this period (Clark 1977b). It has yet to be ascertained whether the nature of this protection is the same as that expressed when pretreated mice first encounter this parasite.…”

“…The highest dose of cord factor provided some protection, but the two lower doses none (Figure la). Since we had earlier shown that increasing the interval between injection of BCG and subsequent injection with B. microti led to greater protection (Clark et al 1977b), the interval between 200 pg of cord factor and lo6 B. microti was also extended. An interval of 5 weeks led to much better protection, and this improved further with a 7-week interval (Figure lb).…”