Effects of Propionibacterium acnes treatment on the course of Mycobacterium leprae infection in mice

Abstract

Studies were carried out to determine the effects of treatment with killed suspensions of Propionibacterium acnes (formerly designated Corynebacterium parvum) on the course of Mycobacterium leprae infection in mice. Systemic (intravenous or intraperitoneal) treatment with P. acnes failed to significantly alter the growth of M. leprae in the mouse footpad. In contrast, injections of P. acnes directly into the infected footpad markedly inhibited the growth of the leprosy bacilli regardless of whether the local treatments were administered before infection or 3 months after infection with M. leprae. The effects of local treatment with P. acnes appeared to be bactericidal and not merely bacteriostatic. Clearance of the organism from the tissues was not enhanced by P. acnes treatment. A large body of evidence attests to the immunopotentiating effects of treatment with suspensions of killed Propionibacterium acnes (formerly designated Corynebacterium parvum [5]). In mice, treatment with P. acnes markedly enhances the function of the reticuloendothelial system (2, 11), increases host resistance to tumors (11, 14, 17, 20-22), and enhances their capacity to resist infection with a variety of pathogenic organisms including Salmonella enteritidis (3), Bordetella pertusis (1), Brucella abortus (1), Plasmodium berghei (18), Toxoplasma gondii (28), and Listeria monocytogenes (28). The present studies were carried out to determine the effects of systemic and local treatment with P. acnes on the growth of Mycobacterium leprae in the mouse footpad. MATERIALS AND METHODS Mce. Locally bred BALB/c mice were used. All of the mice were females and weighed 18 to 22 g at the start of each experiment. P. acnes. A killed suspension of P. acnes (C. parvum, lot no. CA749, 7 mg/ml dry weight) was kindly provided by Richard Tuttle (Burroughs-Wellcome Co., Research Triangle Park, N.C.). P. acnes treatments were administered intravenously (i.v.), intraperitoneally (i.p.), or subcutaneously (s.c.) in the groin area or s.c. into the hind footpad. M. kprae infection. Mice were inoculated in the right or both hind footpads (RHF and BHF, respectively [LHF = left hind footpad]) with 5 x 103 M. leprae, and the course of infection was followed at intervals by harvest and enumeration of acid-fast

Intracellular fate of Mycobacterium leprae in normal and activated mouse macrophages

“…The present study demonstrates enhanced lysosome fusion in activated macrophages challenged with M. Ieprae and is consistent with involvement of activated macrophages in bacterial clearance (5,6,22,29). The suspension of freshly harvested M. leprae cells used in the present study was enriched for viability by Percoll gradient purification as determined by ATP content.…”

“…The enormous number of intracellular Mycobacterium leprae organisms within granuloma macrophages of lepromatous leprosy patients (30,31) and infected nude mice (4) indicates that M. leprae survives the microbicidal capacity of normal macrophages. Indirect evidence suggests that activation of macrophages for nonspecific microbicidal activity leads to killing and clearance of M. leprae in mice (22) and in human patients (5,6,29). Among the microorganisms which survive in mononuclear phagocytes by interfering with digestive processing, Mycobacterium tuberculosis (1), Legionella pneumophila (16), and Toxoplasma gondii (20) all reside in modified phagosomes that resist fusion with host cell lysosomes.…”

Leprosy.

“…Although there is some evidence that macrophages from LL patients are deficient in their ability to digest M. leprae (12), not all workers have found such deficiencies (52,197). Our own studies showed that mice with potent populations of activated macrophages were markedly resistant to footpad infection with M. Ieprae (120,121). In other indirect studies, oxidative metabolism of patient phagocytes was tested and found to be normal or above normal (68,76,133).…”

Effects of activated macrophages on Mycobacterium leprae

“…However, other studies of the innate microbicidal properties of LL patients' mononuclear phagocytes for other intracellular pathogens (6) (5,14,15,19,24) and would have proven to be of little value in our relatively short-term in vitro studies. In unpublished preliminary studies, we used the footpad technique to evaluate the effects of activated M4 on M. leprae In other studies, we used the mouse footpad technique and showed that mice with potent populations of activated M4 or mice treated locally with immunopotentiators were markedly resistant to footpad infection with M. leprae (16,17). Others have used the uptake of radiolabelled markers by M. leprae in M4) as a means of quantitating metabolism and studying the effects of antileprosy drugs in vitro (22,28), but we were unable to obtain satisfactory results with these procedures (unpublished results).…”

“…Activated M+. Activated peritoneal M4i were obtained from mice chronically infected with the C-56 strain of Toxoplasma gondii (42) or from mice injected intraperitoneally with 700 ,ug of killed Corynebacterium parvum (Burroughs Wellcome, Inc., Research Triangle Park, N.C.) 7 to 14 days previously (16). The activation of normal M4 was achieved by treatment in vitro with murine recombinant gamma interferon (MuIFN-y; Genentech, Inc., South San Francisco, Calif.) 18 h prior to infection or, in certain experiments, immediately after infection.…”