Suppressor Macrophages in Trypanosoma-Brucei Infection: Nitric Oxide is related to both suppressive activity and life-span in-vivo

N A Mabbott, I A Sutherland, Jeremy M Sternberg

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

African trypanosome infections cause immunosuppression in both experimental rodent and natural hosts. One characteristic of this is an eliciting of suppressor macrophages which results in an unresponsiveness in lymphocytes. Macrophages from Trypanosoma brucei-infected mice have previously been shown to produce high levels of nitric oxide (NO). Using model systems based on in vivo macrophage transfer and drug cure, we have sought to determine the relationship between NO and suppressed lymphocyte responses. Peritoneal macrophages from T. brucei-infected mice inhibited the Concanavalin A (ConA) response of spleen cells from syngeneic recipients 3-4 days after transfer in vivo due to the activity of suppressor macrophages. When macrophage NO synthesis was inhibited either in vitro or in vivo the suppressive effects were partially abrogated. These data provide evidence of a role far NO in mediating immunosuppression during murine T. brucei infection. Suppression in spleens of mice receiving suppressor macrophages was transient, with total recovery of spleen cell mitogen responses six days after transfer. Suppression and recovery was found to coincide with the presence or absence (respectively) of donor macrophages in recipient spleens. When T. brucei-infected mice were treated with a curative dose of a trypanocide there followed a recovery of lymphocyte responsiveness after a period of 4-5 days, and this directly correlated with a reduction of macrophage NO synthesis to control levels bath in vivo and in vitro. The apparent loss of suppressor macrophage activity after 4-6 days in both drug cured animals and recipients of macrophage transfer was shown to be due to NO-mediated apoptosis of these cells.

Original languageEnglish
Pages (from-to)143-150
Number of pages8
JournalParasite Immunology
Volume17
Issue number3
Publication statusPublished - Mar 1995

Keywords

  • MACROPHAGE
  • NITRIC OXIDE
  • IMMUNOSUPPRESSION
  • TRYPANOSOMA BRUCEI
  • T-CELL RESPONSES
  • AFRICAN TRYPANOSOMIASIS
  • ACTIVATED MACROPHAGES
  • APOPTOSIS
  • MICE
  • RHODESIENSE
  • INHIBITION
  • INDUCTION
  • KINETICS
  • macrophage
  • nitric oxide
  • immunosuppression
  • trypanosoma-brucei

Cite this