Schistosoma antigens downmodulate the in vitro inflammatory response in individuals infected with human T cell lymphotropic virus type 1.

UNLABELLED: Human T cell lymphotropic virus type 1 (HTLV-1) is the causal agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). While the immune response to HTLV-1 infection is polarized to the Th1-type, chronic helminth infections drive the Th2- and T regulatory-type, and are able to downregulate the inflammatory response in some autoimmune diseases. OBJECTIVE: To evaluate whether Schistosoma spp. antigens alter the in vitro cytokine response in HTLV-1 infection. METHODS: The recombinant Schistosoma antigens Sm29 and ShTSP2 (tetraspanin) and PIII, a fraction of the Schistosoma mansoni adult worm antigen were added to peripheral blood mononuclear cell (PBMC) cultures of HTLV-1-infected individuals and the levels of interferon (IFN)-γ and interleukin (IL)-10 in the supernatants were measured using the ELISA sandwich technique. RESULTS: Compared to the levels of cytokine in nonstimulated cultures, the levels of IFN-γ were reduced in 50, 47 and 50% of patients by the presence of Sm29, ShTsp2 and PIII, respectively. The downregulation of IFN-γ production in the presence of Sm29 antigen was observed mainly in subjects who had lower basal levels of this cytokine. The levels of IL-10, however, increased by the addition of the three antigens in the cultures in 74, 62 and 44% of individuals, respectively. In addition, there was a decrease in the ratio of IFN-γ/IL-10 levels in cultures stimulated with Sm29 and ShTSP2 when compared to nonstimulated ones. CONCLUSIONS: The Schistosoma spp. antigens used in this study were able to downmodulate IFN-γ production in vitro in HTLV-1 infection. This may be associated with the increased levels of IL-10 induced by the antigens.

Schistosoma antigens downregulate CXCL9 production by PBMC of HTLV-1-infected individuals.

HTLV-1 is the causal agent of Adult T cell Leukemia/lymphoma (ATLL) and HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). The immune response to HTLV-1-infection is polarized to the Th1-type, and the presence of CXCL9/CXCL10 chemokines may lead to an increase in the recruitment of pro-inflammatory molecules in spinal cord tissue, contributing to the damage observed in the development of HAM/TSP. It has been observed that in chronic helminth-infections, such as schistosomiasis, there is a deviation toward the Th2/regulatory immune response. OBJECTIVE: To evaluate the ability of Schistosoma spp. proteins to decrease the in vitro CXCL9 and CXCL10 production by PBMC of HTLV-1-infected individuals. METHODS: The Schistosoma proteins rSm29, rSh-TSP-2 and PIII were added to PBMC cultures of HTLV-1-infected individuals and the levels of chemokines in the supernatants were measured using a sandwich ELISA method. RESULTS: The addition of rSm29 to the cultures resulted in decreased production of CXCL9 in all the analyzed individuals and HAM/TSP group (18167±9727pg/mL, p=0.044; 20237±6023pg/mL, p=0.028, respectively) compared to the levels in unstimulated cultures (19745±9729pg/mL; 25078±2392pg/mL, respectively). The addition of rSh-TSP-2 decreased the production of CXCL9 in all studied individuals and carriers group (16136±9233pg/mL, p=0.031; 13977±8857pg/mL, p=0.026) vs unstimulated cultures (19745±9729pg/mL; 18121±10508pg/mL, respectively). Addition of PIII did not alter the results. There was no significant change in the levels of CXCL10 by the addition of the studied proteins. CONCLUSION: The Schistosoma proteins used in this study were able to down modulate the production of CXCL9, a chemokine associated with the inflammatory process in HTLV-1-infection.