Schistosoma antigens downregulate CXCL9 production by PBMC of HTLV-1-infected individuals
Abstract 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. Highlights Schistosoma antigens rSm29 and rSh-TSP-2 reduce the levels of CXCL9 in supernatants of PBMCs of individuals with HTLV-1. Schistosoma Antigens downregulate the levels of CXCL9 and induced high level of IL-10 in PBMC culture of HTLV-1-infected individuals. Schistosoma antigens are able to supress in vitro the levels os proinflammatory chemokines involved in the pathology of HTLV-1 infection.
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- DOI : http://dx.doi.org/10.1016/j.actatropica.2016.12.030
- Elsevier : 저널> 권호 > 논문
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