Cell-mediated Immunity to Toxoplasma Gondii: Initiation, Regulation and Effector Function

Immunobiology. 1999 Dec;201(2):240-7. doi: 10.1016/S0171-2985(99)80064-3.

Abstract

Cell-mediated immune responses are essential for host control of intracellular infections. Toxoplasma gondii is a protozoan parasite that infects multiple vertebrate species and invades multiple cell types. Upon initial encounter with the immune system, the parasite rapidly induces production of the type-1 promoting cytokine IL-12 most likely from a subpopulation of dendritic cells. NK and T cells are then activated and triggered to synthesize IFN-gamma, the major mediator of host resistance during the acute and chronic phases of infection. During the acute phase, a concomitant IL-10 response dampens the systemic type-1 cytokine production and prevents lethal immunopathology. Cytokine (IFN-gamma und TNF-alpha) rather than cytotoxicity-based effector functions are more critical for protective immunity both during the acute and chronic phases of T. gondii infection. Both hemopoietic and non-hemopoietic cellular elements act as IFN-gamma and TNF-dependent effectors of host resistance. Type II iNOS-derived nitric oxide (NO) is required mainly for hemopoietic cell-derived effector cell activity in the central nervous system (CNS) during the chronic phase of infection. Nevertheless, in both the acute and chronic stages, IFN-gamma-dependent but iNOS-independent mechanism(s) play a major function in parasite control and their identification remains an important challenge for this field.

Publication types

  • Review

MeSH terms

  • Acute Disease
  • Animals
  • Chronic Disease
  • Dendritic Cells / metabolism
  • Humans
  • Immunity, Cellular
  • Interferon-gamma / physiology
  • Interleukin-10 / physiology
  • Interleukin-12 / physiology
  • Killer Cells, Natural / metabolism
  • Lymphocyte Subsets / metabolism
  • Nitric Oxide Synthase / physiology
  • Nitric Oxide Synthase Type II
  • T-Lymphocytes / metabolism
  • Toxoplasma / immunology*
  • Toxoplasmosis / immunology*
  • Toxoplasmosis / parasitology
  • Toxoplasmosis, Animal / immunology*
  • Toxoplasmosis, Animal / parasitology
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Interferon-gamma
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II