Enzimatically active and inactive Trypanosoma cruzi trans-sialidases reduce T CD4+ lymphocyte responses

BOGLIOTTI Y; MUCCI J; CAMPETELLA O

Viña del mar, Chile

Congreso; 9th Latin American Congress of Immunology; 2009

Latin American Association of Innmunology

Enzimatically active and inactive Trypanosoma cruzi trans-sialidases reduce T CD4+ lymphocyte responses. Yanina Bogliotti, Juan Mucci and Oscar Campetella. Instituto de Investigaciones Biotecnológicas (IIB-UNSAM), Buenos Aires, Argentina. yani84@gmail.com.ar Trypanosoma cruzi is the causative agent of Chagas disease. The parasite expresses a family of proteins known as trans-sialidases (TSs), which are involved in numerous events associated in the pathogenicity of the disease. TS transfers [alpha]-2,3-linked sialyl-residues from glycoconjugates to terminal [beta]-1,4-linked galactoses on the parasite mucins and lymphocyte surface molecules. Enzymatically inactive TSs retains a lectin-like function by binding to the substrate. In this work, we analyzed the effect of active and inactive enzymes on T lymphocytes. A marked reduction on proliferation of antigen stimulated DO11.10 splenocytes was observed when treated with either TSs. The detrimental effect was even stronger in cells treated with the inactive molecule. The same result was also obtained when assaying IL-2 secretion by the DO11.10 hybridoma co-cultured with the cognate peptide and A20 as presenting cells, an effect that was not mimicked when anti-CD3 stimulation was tested. Moreover, decrease on the phospho-ZAP-70 signaling in TS-treated DO11.10 splenocytes was also detected implying a reduction of the activation of these cells. These results indicate that both active and inactive TSs downregulate CD4 T cells activities and involve these parasite virulence factors in the evasion of the immune response, helping the host colonization.