African trypanosome infections in mice that lack the interferon-gamma receptor gene: nitric oxide-dependent and -independent suppression of T-cell proliferative responses and the development of anaemia

N A Mabbott, P S Coulson, L E Smythies, Ruth Wilson, Jeremy M Sternberg

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35 Citations (Scopus)

Abstract

Infection of mice with African trypanosomes leads to a severe immunosuppression, mediated by suppressor macrophages. Using ex vivo macrophage culture and in vivo cell transfer, it has been shown that nitric oxide (NO) is a potent effector product of these cells and causes both lymphocyte unresponsiveness and dyserythropoiesis. We explored the role of NO in vivo during trypanosome infection using mice with a disrupted interferon-gamma-receptor gene, which were unable to respond with macrophage activation and NO synthesis. These mice were less effective at controlling parasitaemia than the wild types, but showed an improved splenic T-cell responsiveness and reduced anaemia during the early stages of infection. The data indicate that, in the mouse, NO is a significant mediator of immunosuppression only in early infection. Beyond day 10 of infection, NO-independent mechanisms are of primary significance and the control of parasitaemia and T-cell responsiveness are not directly related.

Original languageEnglish
Pages (from-to)476-480
Number of pages5
JournalImmunology
Volume94
Issue number4
DOIs
Publication statusPublished - Aug 1998

Keywords

  • VARIANT SURFACE GLYCOPROTEIN
  • BRUCEI INFECTION
  • IN-VIVO
  • MACROPHAGES
  • INHIBITION
  • GENERATION
  • INDUCTION
  • SYNTHASE
  • ANTIGEN
  • GROWTH

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