Lymphocyte-Macrophage Interaction during Control of Intracellular Parasitism *

Jones, Thomas C.; Masur, Henry; Len, L; Fu, Tzu Lin Tom

doi:10.4269/ajtmh.1977.26.187

Cited by 21 publications

(13 citation statements)

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“…TIVITY. In contrast to the preceding lymphokine experiments, cocultivation with HIB and toxoplasma lymphokine for 18 h before infection renders normal macrophages as effective as IM cells in inhibiting parasite multiplication (13). HIB alone has no effect.…”

Section: Role Of Oxygen Intermediates In Lymphokine Hib-induced Antitmentioning

confidence: 75%

“…The molecular basis underlying the synergistic action of HIB and lymphokines has not been investigated, but may be related to the presence of endotoxin (36). Thus, in this system, HIB can be replaced by endotoxin (13), as well as THIO (13) or PP, and BCG and Con A supernates can substitute for toxoplasma lymphokine (H. Murray. Unpublished observations).…”

Section: Discussionmentioning

confidence: 99%

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Macrophage oxygen-dependent antimicrobial activity. III. Enhanced oxidative metabolism as an expression of macrophage activation.

Murray¹,

Cohn²

1980

The Journal of Experimental Medicine

198

125

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In previous reports (1, 2) we demonstrated that Toxoplasma gondii, an obligate intracellular parasite, is susceptible to oxygen intermediates generated by the partial reduction of molecular oxygen. In a cell-free model, toxoplasmas are resistant to superoxide anion (O~-) and hydrogen peroxide (H202), but are readily killed by toxic products of O~-H202 interaction, presumably hydroxyl radical (OH-) and singlet oxygen (102) (1). We also implicated these latter two oxygen intermediates as probable mediators of the toxoplasmastatic and toxoplasmacidal activity of specifically immune peritoneal macrophages (2).The present study extends these observations by examining in parallel the antitoxoplasma activity and oxidative capacity of peritoneal cells stimulated in vivo by inflammatory and immunologic agents, and in vitro by soluble products of sensitized lymphocytes (lymphokines). We have, thus, been able to characterize a spectrum of activated macrophages that differ quantitatively in their production of O~-and H202, and their capacity to carry out an intracellular anti-microbial act. Our observations also reemphasize the importance of macrophage oxygen-dependent antimicrobial mechanisms in both the in vivo and in vitro activated state. Materials and MethodsParasites. The virulent RH strain and the nonvirulent Pe strain of Toxoplasma gondii were maintained and harvested as previously reported (1). RH strain toxoplasma trophozoites were used to infect cultivated macrophages, whereas Pe strain brain cysts were used to produce chronically infected toxoplasma immune mice (2).Macrophages. Normal macrophages were obtained from female NCS mice (The Rockefeller University, New York). Toxoplasma-immune macrophages (IM) 1 and immune-boosted macrophages (IB) were from NCS mice infected 3-8 wk before the Pe brain cysts. Immune-boosted mice received 5 × 106 heat-killed RH toxoplasma trophozoites intraperitoneally 3 d before harvest (2). Other NCS mice were injected intravenously or intraperitoneally with 2 × 107 * Supported by grants 1 732 GM-07247 and AI-07012 from the U. S. Public I~tealth Service, and The Rockefeller Foundation Grant GAllS 7716.:~ Present address: Cornell University Medical College, New York 10021. 'Abbreviations used in this paper: BCG, Bacille Calmette-Gu~rin, Con A, concanavalin A; DABCO, diazabicyclooctane; D20HIFBS, Dulbecco's medium containing 20% heat-inactivated FBS, penicillin, and streptomycin; FBS, fetal bovine serum; HIB, heart infusion broth; IB, toxoplasma immune-boosted; IM, toxoplasma-immune; NBT, nitroblue tetrazolium; PBS, phosphate-buffered saline; PMA, phorbol myrisrate acetate; PP, proteose peptone; SOD, superoxide dismutase; THIO, thioglycollate. 1596J. ExP. MED.

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Section: Role Of Oxygen Intermediates In Lymphokine Hib-induced Antitmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Macrophage oxygen-dependent antimicrobial activity. III. Enhanced oxidative metabolism as an expression of macrophage activation.

Murray¹,

Cohn²

1980

The Journal of Experimental Medicine

198

125

View full text Add to dashboard Cite

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“…Moreover, pretreatment ofmacrophages with our lymphokine preparations fails to elicit leishmanicidal activity of these phagocytes, in contrast to the action of antitrypanosome (24) and antitoxoplasma (18) lymphokines. Furthermore, the activity ofour lymphokine preparations is unaffected by prior treatment of macrophages with trypsin or neuraminidase, whereas these treatments are known to abolish the activities of other antiparasite lymphokines (17,18). This suggests that the mode ofaction of lymphokine-mediated leishmanicidal activity in our system may be independent of lymphocyte mediator-macrophage receptor interactions.…”

mentioning

confidence: 59%

“…Continuous treatment ofinfected macrophages by the lymphokines for at least 3 days or more is required in our system for the manifestation ofleishmanicidal activity. This is somewhat analogous to the action of lymphokines on mycobacteria in mouse macrophages (21) but differs from that of all the other antiparasitic lymphokines, which produce a more drastic effect in less than 3 days against other protozoa including cutaneous leishmanias (11,12,18,19,(22)(23)(24). Moreover, pretreatment ofmacrophages with our lymphokine preparations fails to elicit leishmanicidal activity of these phagocytes, in contrast to the action of antitrypanosome (24) and antitoxoplasma (18) lymphokines.…”

mentioning

confidence: 99%

Cellular immunity of mice to Leishmania donovani in vitro: lymphokine-mediated killing of intracellular parasites in macrophages.

Chang¹,

Chiao²

1981

Proc. Natl. Acad. Sci. U.S.A.

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Leishmania doovani, an intracellular protozoan, causes kala-azar by parasitizing the macrophages ofits mammalian host. Outbred NCS and CD-i mice develop immunity to this parasite. This immunity was demonstrable when supernatant fluids from cultured splenic lymphocytes were added to infected macrophages. Only the lympholdne preparations from infected mice showed significant leishmanicidal activity. Mice receiving multiple inocula-were more potent producers of leishmanicidal lymphokines than were those receiving single inocula. The expression of leishmanicidal activity in our system required continuous presence of the lympholdne preparation and was independent of trypsin-or neuraminidase-sensitive receptors ofthe macrophages. Light and electron microscopy revealed that, in the presence of lymphokines, macrophages appeared to be "activated," and intraceliular leishmanias developed specific subcellular lesions in the kdnetoplast-mitochondria. A time-course study showed that cultivation of the lymphocytes for 1/2 days completed the release of their leishmanicidal lympholdnes which were heat-labile molecules larger than 50,000 daltons.Leishmanias are trypanosomatid protozoa whose amastigote stage parasitizes the mononuclear series ofthe reticuloendothelial system, resulting in leishmaniasis. In response to infection by different species, susceptible hosts manifest distinct clinical symptoms ranging from self-curing cutaneous lesions to an often-fatal visceral form (1). Immunity of all species of animals is thought to be largely cell-mediated, but supporting evidence for this has been derived from investigations ofthe experimental cutaneous leishmaniases (2, 3). The work of Skov and Twohy (4,5) provided in vivo evidence for the importance of thymusderived lymphocytes in mouse immunity to visceral leishmania (Leishmania donovani).We now provide evidence for the expression ofthis immunity in vitro by soluble lymphokine factors released by splenic lymphocytes derived from infected mice. Some properties of these factors and their effects on intracellular leishmanias in macrophages are characterized. MATERIALS AND METHODSAll chemicals and medium components were purchased from Sigma and GIBCO, respectively.Animals. Outbred NCS and CD-1 mice (at least 25 g in body weight) raised under conventional conditions at the Rockefeller University or Sloan-Kettering Cancer Research Center were used for the present study. Both strains of mice developed immunity to L. donovani, as indicated by examining the parasite burden during the course ofinfection. The number ofparasites in both liver and spleen increased during the initial 30 days and remained stable thereafter.Parasites. Amastigotes ofL. donovani, Sudan-IS strain, were obtained from spleens of Syrian golden hamsters infected intracardially 1-2 months earlier. Isolated amastigotes were intact, viable, and free from host cell contamination (6, 7).Infection of Mice. Aliquots of the amastigote suspension in Hanks' balanced salt solution were injected intraveneously at 50 X 10...

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“…Macrophages have a decreased rate of pinocytosis [18] rather than increased as within elicited cells, and they demonstrate primarily toxoplasmastatic properties. The initiation of this toxoplasmastatic response in macrophages is associated with changes in cyclic nucleotides in the cell and it is blocked by corticosteroids as well as inhibitors of protein synthesis [20]. They do not show increase in lysosome-phagosome fusion [19].…”

Section: Correlates Of the Immune Response Duringtoxoplasmosismentioning

confidence: 98%