Mechanisms of innate resistance to Toxoplasma gondii infection

J. Alexander, T. M. Scharton-Kersten, G. Yap, C. W. Roberts, F. Y. Liew, A. Sher

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

The interaction of protozoan parasites with innate host defences is critical in determining the character of the subsequent infection. The initial steps in the encounter of Toxoplasma gondii with the vertebrate immune system provide a striking example of this important aspect of the host-parasite relationship. In immunocompetent individuals this intracellular protozoan produces an asymptomatic chronic infection as part of its strategy for transmission. Nevertheless, T. gondii is inherently a highly virulent pathogen. The rapid induction by the parasite of a potent cell-mediated immune response that both limits its growth and drives conversion to a dormant cyst stage explains this apparent paradox. Studies with gene-deficient mice have demonstrated the interleukin-12 (IL-12)-dependent production of interferon γ (IFN-γ) to be of paramount importance in controlling early parasite growth. However, this seems to be independent of nitric oxide production as mice deficient in inducible nitric oxide synthase (iNOS) and tumour necrosis factor receptor were able to control early growth of T. gondii, although they later succumbed to infection. Nitric oxide does, however, seem to be important in controlling persistent infection; treating chronic infection with iNOS metabolic inhibitors results in disease reactivation. Preliminary evidence implicates neutrophils in effector pathways against this parasite distinct from that described for macrophages. Once initiated, IL-12-dependent IFN-γ production in synergy with other proinflammatory cytokines can positively feed back on itself to induce 'cytokine shock'. Regulatory cytokines, particularly IL-10, are essential to down-regulate inflammation and limit host pathology.

Original languageEnglish
Pages (from-to)1355-1359
Number of pages5
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume352
Issue number1359
DOIs
Publication statusPublished - 1 Jan 1997

Keywords

  • toxoplasma gondii
  • innate resistance
  • protozoan parasites
  • vertebrate immune system

Fingerprint Dive into the research topics of 'Mechanisms of innate resistance to Toxoplasma gondii infection'. Together they form a unique fingerprint.

Cite this