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J Exp Med. Jul 1, 1975; 142(1): 1–16.
PMCID: PMC2189870

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

Abstract

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.

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Selected References

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  • Armstrong JA, Hart PD. Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of lysosomes with phagosomes. J Exp Med. 1971 Sep 1;134(3 Pt 1):713–740. [PMC free article] [PubMed]
  • Hart PD, Armstrong JA, Brown CA, Draper P. Ultrastructural study of the behavior of macrophages toward parasitic mycobacteria. Infect Immun. 1972 May;5(5):803–807. [PMC free article] [PubMed]
  • Friis RR. Interaction of L cells and Chlamydia psittaci: entry of the parasite and host responses to its development. J Bacteriol. 1972 May;110(2):706–721. [PMC free article] [PubMed]
  • Lawn AM, Blyth WA, Taverne J. Interactions of TRIC agents with macrophages and BHK-21 cells observed by electron microscopy. J Hyg (Lond) 1973 Sep;71(3):515–528. [PMC free article] [PubMed]
  • Jones TC, Hirsch JG. The interaction between Toxoplasma gondii and mammalian cells. II. The absence of lysosomal fusion with phagocytic vacuoles containing living parasites. J Exp Med. 1972 Nov 1;136(5):1173–1194. [PMC free article] [PubMed]
  • Evans MJ, Newton HE, Levy L. Early response of mouse foot pads to Mycobacterium laprae. Infect Immun. 1973 Jan;7(1):76–85. [PMC free article] [PubMed]
  • Allison AC, Hart PD. Potentiation by silica of the growth of Mycobacterium tuberculosis in macrophage cultures. Br J Exp Pathol. 1968 Oct;49(5):465–476. [PMC free article] [PubMed]
  • Hart PD. Mycobacterium tuberculosis in macrophages: effect of certain surfactants and other membrane-active compounds. Science. 1968 Nov 8;162(3854):686–689. [PubMed]
  • Hirsch JG, Fedorko ME. Ultrastructure of human leukocytes after simultaneous fixation with glutaraldehyde and osmium tetroxide and "postfixation" in uranyl acetate. J Cell Biol. 1968 Sep;38(3):615–627. [PMC free article] [PubMed]
  • Hart PD, Armstrong JA. Strain virulence and the lysosomal response in macrophages infected with Mycobacterium tuberculosis. Infect Immun. 1974 Oct;10(4):742–746. [PMC free article] [PubMed]
  • Stewart-Tull DE, Wilkinson PC. The affinity of mycobacterial glycopetides for guinea-pig gamma immunoglobulin and its fragments. Immunology. 1973 Aug;25(2):205–216. [PMC free article] [PubMed]
  • Edelson PJ, Cohn ZA. Effects of concanavalin A on mouse peritoneal macrophages. I. Stimulation of endocytic activity and inhibition of phago-lysosome formation. J Exp Med. 1974 Nov 1;140(5):1364–1386. [PMC free article] [PubMed]
  • Edelson PJ, Cohn ZA. Effects of concanavalin A on mouse peritoneal macrophages. II. Metabolism of endocytized proteins and reversibility of the effects by mannose. J Exp Med. 1974 Nov 1;140(5):1387–1403. [PMC free article] [PubMed]
  • GELZER J, SUTER E. The effect of antibody on intracellular parasitism of Salmonella typhimurium in mononuclear phagocytes in vitro: prolonged survival of infected monocytes in presence of antibody. J Exp Med. 1959 Nov 1;110:715–730. [PMC free article] [PubMed]
  • COHN ZA. The fate of bacteria within phagocytic cells. II. The modification of intracellular degradation. J Exp Med. 1963 Jan 1;117:43–53. [PMC free article] [PubMed]
  • FONG J, CHIN D, AKIYAMA HJ, ELBERG SS. Studies on tubercle bacillus-monocyte relationship. III. Conditions affecting the action of serum and cells; modification of bacilli in an immune system. J Exp Med. 1959 Jun 1;109(6):523–543. [PMC free article] [PubMed]
  • ROWLEY D. Bactericidal activity of macrophages in vitro against Escherichia coli. Nature. 1958 Jun 21;181(4625):1738–1739. [PubMed]
  • JENKIN C, BENACERRAF B. In vitro studies on the interaction between mouse peritoneal macrophages and strains of Salmonella and Escherichia coli. J Exp Med. 1960 Aug 1;112:403–417. [PMC free article] [PubMed]
  • Hard GC. Examination by electron microscopy of the interaction between peritoneal phagocytes and Corynebacterium ovis. J Med Microbiol. 1972 Nov;5(4):483–491. [PubMed]
  • Gambrill MR, Wisseman CL., Jr Mechanisms of immunity in typhus infections. 3. Influence of human immune serum and complement on the fate of Rickettsia mooseri within the human macrophages. Infect Immun. 1973 Oct;8(4):631–640. [PMC free article] [PubMed]
  • Anderson SE, Jr, Remington JS. Effect of normal and activated human macrophages on Toxoplasma gondii. J Exp Med. 1974 May 1;139(5):1154–1174. [PMC free article] [PubMed]
  • Jones TC. Macrophages and intracellular parasitism. J Reticuloendothel Soc. 1974 May;15(5):439–450. [PubMed]
  • Jones TC, Len L, Hirsch JG. Assessment in vitro of immunity against Toxoplasma gondii. J Exp Med. 1975 Feb 1;141(2):466–482. [PMC free article] [PubMed]
  • Ando M, Dannenberg AM., Jr Macrophage accumulation, division, maturation, and digestive and microbicidal capacities in tuberculous lesions. IV. Macrophage turnover, lysosomal enzymes, and division in healing lesions. Lab Invest. 1972 Nov;27(5):466–472. [PubMed]
  • Kochan I, Pellis NR, Pfohl DG. Effects of normal and activated cell fractions on the growth of tubercle bacilli. Infect Immun. 1972 Aug;6(2):142–148. [PMC free article] [PubMed]
  • Patterson RJ, Youmans GP. Demonstration in tissue culture of lymphocyte-mediated immunity to tuberculosis. Infect Immun. 1970 Jun;1(6):600–603. [PMC free article] [PubMed]
  • Klun CL, Youmans GP. The effect of lymphocyte supernatant fluids on the intracellular growth of virulent tubercle bacilli. J Reticuloendothel Soc. 1973 Mar;13(3):263–274. [PubMed]

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