TY - JOUR
T1 - Identification of a parasitic immunomodulatory protein triggering the development of suppressive M1 macrophages during African trypanosomiasis
AU - Gómez-Rodríguez, Julio
AU - Stijlemans, Benoit
AU - De Muylder, Géraldine
AU - Korf, Hannelie
AU - Brys, Lea
AU - Berberof, Magali
AU - Darji, Ayub
AU - Pays, Etienne
AU - De Baetselier, Patrick
AU - Beschin, Alain
PY - 2009/12/1
Y1 - 2009/12/1
N2 - 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 γ, 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. © 2009 by the Infectious Diseases Society of America. All rights reserved.
AB - 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 γ, 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. © 2009 by the Infectious Diseases Society of America. All rights reserved.
U2 - 10.1086/648374
DO - 10.1086/648374
M3 - Article
VL - 200
SP - 1849
EP - 1860
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 12
ER -