How protozoa evade intracellular killing Academic Article uri icon


MeSH Major

  • Eukaryota
  • Macrophages


  • Once swept inside a polymorphonuclear or mononuclear leukocyte and enclosed within a phagocytic vacuole, ingested microorganisms are immediately confronted with a toxic array of both oxygen-dependent and oxygen-independent microbicidal mechanisms. Phagocytosis not only triggers the generation of lethal oxygen intermediates, including superoxide anion, hydrogen peroxide (H2O2), and hydroxyl radical, but also stimulates cytoplasmic granules and lysosomes to fuse with the pathogen-containing vacuole and discharge their potentially destructive components. In most instances, these mechanisms act swiftly, and intracellular microbial death within this churning milieu is the rule. Certain pathogens, however, escape intravacuolar killing, and successfully convert phagocytic cells into benign environments that perpetuate infection by allowing unimpeded intracellular replication. The capacity to parasitize normal (unstimulated) macrophages, cells that populate most of our tissues, is particularly well illustrated by the protozoa, Toxoplasma gondii, Leishmania species, and Trypanosoma cruzi - the etiologic agents of toxoplasmosis, visceral and cutaneous leishmaniasis, and Chagas' disease. Three mechanisms may explain how these pathogens accomplish intracellular parasitism: The parasites are innately resistant to the phagocyte antimicrobial responses, they avoid triggering this response during ingestion, or the target macrophage itself is intrinsically deficient in killing capacity. In addition to those studies, which have afforded the opportunity to scrutinize the interaction of invading parasites and host macrophages at the microscopic level, one other related macroscopic feature of infection caused by the intracellular protozoa also deserves mention: the capacity to suppress the host's expected cellular immune response. Thus, in susceptible hosts, it now appears that infection with T. gondii, Leishmania species, and T. cruzi can induce both parasite-specific and nonspecific suppressor mechanisms. Although the cells involved and the molecular basis of this provoked suppressor response appear to be highly variable, a common feature seems to be inhibition of normal T lymphocyte function including, at least in experimental visceral leishmaniasis, the generation of effective macrophage-activating lymphokines. Inhibited T-cell activity and suppression of lymphokine secretion presumably abolish a key stimulus for the amplification of macrophage oxygen-dependent and -independent antiprotozoal mechanisms, and may perpetuate infection by rendering macrophages continually susceptible to parasitization. How protozoan infections induce such self-protective suppressor mechanisms within the host is unknown.

publication date

  • December 1983



  • Academic Article



  • eng

PubMed ID

  • 6344706

Additional Document Info

start page

  • 1016

end page

  • 8


  • 98


  • 6