Conversion of Trypanosoma cruzi Tc52 released factor to a protein inducing apoptosis.
In this study Tc52, a Trypanosoma cruzi released protein, which exerts an immunoregulatory activity, was converted to a molecular form with altered biological function. Indeed, the genetic fusion of Tc52 to a carrier protein, the Shistosoma japonicum glutathione S-transferase (Tc52-Sj26), was shown to induce apoptosis in spleen cells from BALB/c or CBA mice and the human T-cell leukemic cell line (CEM). Cell death by apoptosis was evidenced by the following criteria: (1) increased binding of Annexin V to rTc52-treated spleen cells; (2) the presence of an ordered cleavage of the DNA backbone; (3) double labeling showed increased number of T cells undergoing apoptosis upon incubation with rTc52; (4) the use of a CEM cell line and TUNEL assay allowed to show in situ DNA fragmentation. Surprisingly, intraperitoneal injections of rTc52 to BALB/c mice, which were then infected with T. cruzi, resulted in increased parasiteamia levels and is congruent to 2.5 times increase of macrophages number. Since native Tc52 could not trigger, apoptosis of T cells we could hypothesized that the fusion of Tc52 with Sj26 led to conformational changes resulting in apoptosis inducing properties of rTc52. The possible in vivo physiopathological implications of these finding were discussed.
Borges
M
M
IRD UR 008 Pathogénie des Trypanosomatides, Centre IRD de Montpellier, 911 Av. Agropolis, BP 64501, 34394 Montpellier, France.
Cordeiro-da-Silva
A
A
Vergnes
B
B
Sereno
D
D
Ouaissi
A
A
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D002452:Cell Count; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D014355:Chagas Disease; D053938:DNA Fragmentation; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D018512:Parasitemia; D015800:Protozoan Proteins / Q000378:metabolism* / Q000494:pharmacology; D011994:Recombinant Proteins; D013154:Spleen / Q000166:cytology; D013997:Time Factors; D014349:Trypanosoma cruzi / Q000378:metabolism*
C097550:52-kDa protein, Trypanosoma cruzi; D015800:Protozoan Proteins; D011994:Recombinant Proteins