Identification of a parasitic immunomodulatory protein triggering the development of suppressive M1 macrophages during African trypanosomiasis.
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.
Gómez-Rodríguez
Julio
J
Department of Molecular and Cellular Interactions, Vlaams Institute voor Biotechnologie (VIB), Vrije Universiteit Brussel, 1050 Brussels, Belgium.
Stijlemans
Benoit
B
De Muylder
Géraldine
G
Korf
Hannelie
H
Brys
Lea
L
Berberof
Magali
M
Darji
Ayub
A
Pays
Etienne
E
De Baetselier
Patrick
P
Beschin
Alain
A
D000818:Animals; D049109:Cell Proliferation; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009569:Nitric Oxide / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000276:immunology*; D014353:Trypanosomiasis, African / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015800:Protozoan Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma