Mycobacterium marinum has been recommended as a possible model of M. leprae for use in laboratory studies of antileprosy immunity. M. marinum introduced into the footpads of normal mice underwent a steady decline in viability, with less than 1% survival after a 30-day period. Small numbers of viable bacilli were recovered from the footpads of these mice up to 12 months later. Similarly, mice infected with M. simiae exhibited bacterial populations that persisted for up to 18 months with little change in viability. Injection of M. simiae into the footpads was followed by an extensive redistribution of the organisms in the tissues. Eventually, bacterial counts for footpads and draining lymph nodes stabilized, with small numbers of bacilli still present in the footpads 18 months later. Persistent growth, with little sign of any immune response, was also observed in mice infected with several strains of M. avium, as well as with one strain of M. intracellulare. Other strains of M. intracellulare, as well as M. vaccae and M. nonchromogenicum, failed to establish persistent infections in normal mice, regardless of whether they were introduced by an intravenous or subcutaneous (footpad) route. The relevance of these findings is discussed in relation to antileprosy immunity in experimental animals and in humans.

No abstract

Specific pathogen-free CD-1 mice were infected subcutaneously in the footpad with Mycobacterium kansasii, three strains of M. marinum, and two strains of M. simiae-habana, and the growth of the organisms in the footpad, the draining popliteal lymph node, and the lung and spleen was followed quantitatively for up to 60 days. The ability of a footpad inoculum of M. marinum to spread to the lungs and spleen correlated with the ability of the organism to survive and multiply at 37 C in in vitro cultures. The amount of footpad swelling which developed in the M. kansasii-and M. marinum-infected mice varied depending upon the strain of organism and the size of the original footpad inoculum. Injection of dead M. marinum into the footpad also induced an extensive amount of swelling which varied with the strain used, as well as being dose dependent. M. marinum-and BCG-vaccinated mice were protected against a later footpad challenge with M. marinum or the highly mouse virulent M. tuberculosis strain Erdman. The significance of this finding is discussed in relation to cross-protection studies using a variety of mycobacteria in the footpad infection model.

Normal, specific pathogen-free mice were vaccinated intravenously with increasing amounts of a streptomycin-resistant variety of BCG Tice (BCG SM R ). The behavior of BCG SM R in the lungs, liver, and spleen was followed quantitatively for up to 50 days. One or two intravenous doses of 10 6 viable organisms were steadily eliminated from the tissues without producing detectable tuberculin sensitivity or raising resistance to a subsequent challenge with Mycobacterium tuberculosis strain Erdman. But mice receiving six weekly injections of 10 6 viable BCG SM R or a single injection of 10 6 BCG SM R by the intravenous route did develop effective levels of antituberculous resistance. Heat inactivation of the BCG SM R inoculum removed the organism's protective activity which could, however, be restored by incorporation of the organisms into Freund adjuvant. The ability of living BCG SM R to induce an effective antituberculous resistance when introduced into the tissues in an appropriate manner is discussed in terms of the mechanism of antituberculous immunity.