Identification of a parasitic immunomodulatory protein triggering the development of suppressive M1 macrophages during African trypanosomiasis

Julio Gómez-Rodríguez, Benoit Stijlemans, Géraldine De Muylder, Hannelie Korf, Lea Brys, Magali Berberof, Ayub Darji, Etienne Pays, Patrick De Baetselier, Alain Beschin

Research output: Contribution to journalA1: Web of Science-article

Abstract

Development of classically activated macrophages (M1 cells) is a prerequisite to controlling parasite growth and therefore resistance to African trypanosomiasis. However, if activation of M1 cells is uncontrolled, including their production of tumor necrosis factor (TNF) and nitric oxide (NO), collateral pathogenic damage to tissues ensues. We report the identification of a novel putative Trypanosoma brucei M1 cell-triggering protein. The recombinant trypanosome-suppressive immunomodulating factor (rTSIF) induced TNF and NO secretion by macrophages. Moreover, M1 cells triggered by rTSIF block T cell proliferation in a manner dependent on NO, interferon gamma, and cell contact. Furthermore, rTSIF could down-regulate type 2-oriented immune responses. Therefore, trypanosome-suppressive immunomodulating factor (TSIF) may represent a new parasite molecule with the potential to modulate the host immune network, whereby it could contribute to the inflammatory response required to control parasite growth and to the pathogenicity of African trypanosomiasis, including immunosuppression. TSIF knock-down trypanosomes died within 2 days, indicating that TSIF may be essential for parasite biology.

Original languageEnglish
JournalJournal of Infectious Diseases
Volume200
Issue number12
Pages (from-to)1849-1860
Number of pages12
ISSN0022-1899
DOIs
Publication statusPublished - 2009

Keywords

  • Animals
  • Cell Proliferation
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Immune Tolerance
  • Interferon-gamma
  • Macrophages
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Nitric Oxide
  • Protozoan Proteins
  • T-Lymphocytes
  • Trypanosoma brucei brucei
  • Trypanosomiasis, African
  • Tumor Necrosis Factor-alpha
  • Journal Article
  • Research Support, Non-U.S. Gov't

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