Tubercle bacilli of the pathogenic human strain H37Rv had previously been shown to multiply, after ingestion by cultured mouse peritoneal macrophages, within phagosomes that tended to remain unfused with secondary lysosomes. Means were sought therefore for promoting experimentally a modification of the host response so as to attain a high level of phagolysosome formation, enabling tests to be made of any effects on the course and outcome of the intracellular infection. This was achieved by exposing viable bacilli to specific rabbit antiserum before their ingestion. Quantitative assessments, using electron microscopy, now showed that a majority of the phagosomes containing intact bacilli had fused with ferritin-labeled lysosomes, and frequently the fusion was massive. Bacterial viability studies established that the serum pretreatment was not itsel bactericidal. In the course of progressive infections with strain H37Rv, monitored by counts both of viable bacterial units and of intracellular acid-fast organisms, no appreciable difference was found between the intracellular growth rates of control and antiserum-treated bacilli. Concurrent electron microscopy showed that bacilli could remain intact and multiply both in phaagolysosomes and in unfused phagosomes, ruling out the possibility of selective growth of antiserum-pretreated bacilli within the minority of phagosomes that remained unfused. It was concluded that "turning on" phagosome-lysosome fusion in normal macrophages did not influence the outcome of infection with virulent M. tuberculosis; lysosome contents manifestly failed to exercise an antibacterial effect on this organism. Nevertheless, the possibility remains that the lysosomes of specific immune macrophages have antituberculous potentiality. In that case the experimental "turning on or off" of fusion could be a decisive factor in the outcome of a virulent challenge. Should it not be, the antibacterial capabilities of immune cells would need to be ascribed to factors other than lysosomal attack, the latter being essentially for disposal of the dead organisms.

https://rupress.org/jem/article-pdf/142/1/1/1267442/1.pdf

Phagosome-lysosome interactions in cultured macrophages infected with virulent tubercle bacilli. Reversal of the usual nonfusion pattern and observations on bacterial survival.

The authors argue that plague should be taken much more seriously by the international health community.

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Plague: past, present, and future.

A. Macrophage-Dependent Resistance in the Absence of Specific Immune Responses.... 1223 B. Augmentation of Macrophage Numbers by Local Proliferation and Influx of Monocytes from the Blood 1223 C. Granuloma Formation 1224 D. Macrophage Activation 1224 E. The Genetic Basis of Mononuclear Phagocyte-Dependent Resistance ......... 1226 F. Role of Polymorphonuclear Leukocytes .... 1226

The Role of Cell-Mediated Immunity in Bacterial Infections

Brucellosis vaccines: past, present and future.

(1973). Bacterial Assimilation of iron. CRC Critical Reviews in Microbiology: Vol. 2, No. 3, pp. 273-331.

Bacterial Assimilation of iron

Immunization against Brucella infection. VI. Immunity conferred on goats by a nondependent mutant from a streptomycin-dependent mutant strain of Brucella melitensis.

In 1976, in a small, remote Libyan village, one apparently sick camel was slaughtered and skinned, and the camel meat was distributed for human comsumption. A few days later, 15 villagers suffered a severe febrile illness. Of the five individuals who had participated in the killing and dispensation of the camel, all were dead within four days. When samples of serum from nine of the remaining patients were examined, seven were found to be positive for plague as determined by the passive hemagglutination test. Another six persons became ill after killing two goats, and the serum of one goat contained antibodies to Yersinia pestis. Because all of the remaining patients except one were treated early enough, they recovered. These incidents confirm previous reports that the camel and the goat are susceptible to naturally occurring plague infection and have a significant role in the dissemination of human plague.

Plague in Camels and Goats: Their Role in Human Epidemics

A non-specific element has been demonstrated in the resistance of monocytes derived from immunized rabbits. Vaccination by BCG or by an effective anti-brucellosis reagent induces protection in either case against both Mycobacterium tuberculosis and Brucella melitensis when studied by the monocyte culture method.

The activity of the antiserum required to demonstrate the resistance of the monocyte is not affected when the agglutinating action of the anti- Brucella rabbit serum is removed by absorption.

The ability of the monocytes from specifically immunized rabbits to retard the growth of virulent Brucella was demonstrated, not as an all-or-none phenomenon, but in the light of the unrestricted bacterial multiplication which occurs in monocytes from normal animals.

https://rupress.org/jem/article-pdf/106/4/545/1391122/545.pdf

Cross-Immunity between Brucella melitensis and Mycobacterium tuberculosis. Intracellular Behavior of Brucella melitensis in Monocytes from Vaccinated Animals.

Studies of the conditions necessary for maintenance of constant cell populations in vitro in the Mackaness type of culture chamber have indicated the importance of preliminary trypsinization of cells and the beneficial effect of 40 per cent rabbit serum in Tyrode's solution Under these optimal conditions, uninfected suspensions of monocytes exhibited little change in cell numbers over a period of 40 to 72 hours Infection of monocytes with the virulent H37Rv strain of tubercle bacillus resulted in an early degeneration of a certain proportion of the cells cultivated in the presence of normal rabbit serum This degeneration was apparent not only for cells of tuberculin-negative animals but also for those derived from tuberculin-positive animals The serum of animals vaccinated with BCG exerted a favorable effect upon the survival of monocytes infected with virulent tubercle bacilli Treatment with this serum caused a delay in degeneration of infected normal cells (cells of tuberculin-negative rabbits) and a complete inhibition of degeneration of infected immune cells (cells of rabbits vaccinated with BCG)

/pdf/studies-on-tubercle-bacillus-monocyte-relationship-i-1txwwuvbn9.pdf

Studies on tubercle bacillus-monocyte relationship : i. quantitative analysis of effect of serum of animals vaccinated with bcg upon bacterium-monocyte system

Sanford S. Elberg

Papers

Immunization against Brucella infection. VI. Immunity conferred on goats by a nondependent mutant from a streptomycin-dependent mutant strain of Brucella melitensis.

Plague in Camels and Goats: Their Role in Human Epidemics

Cross-Immunity between Brucella melitensis and Mycobacterium tuberculosis. Intracellular Behavior of Brucella melitensis in Monocytes from Vaccinated Animals.

Studies on tubercle bacillus-monocyte relationship : i. quantitative analysis of effect of serum of animals vaccinated with bcg upon bacterium-monocyte system

Certain characteristics of the fatty acids from the lipides of the tubercle bacillus.