Effects of Strongyloides stercoralis antigens on immune responses in dendritic cells

Abstract

Strongyloidiasis is a parasitic disease caused by Strongyloides stercoralis. Infection in the immunocompromised hosts such as organ transplants, SLE patients, or HIV and HIPV infected patients can cause severe strongyloidiasis. Infected patients have high levels of Th2, and Treg related cytokines, including IL-4, IL-5, IL-9, IL-10, IL-13, and TGF-β. These cytokines are then decreased to normal levels after the treatments. Parasites have several mechanisms to suppress or evade the host’s immune response, such as suppressing the expression of co-stimulatory molecules on antigen-presenting cells (APCs), stimulating apoptosis of APCs, or stimulating Th2 and Treg responses. Dendritic cells (DCs) play a crucial role in linking the innate and adaptive immune systems against pathogens by engulfing antigens and presenting to naïve T cells with appropriate cytokines. To understand the mechanisms of S. stercoralis to evade the host’s immune responses, we studied the alteration of antigen presentation process and cytokines productions by DCs stimulated with S. stercoralis antigens. We treated DC2.4 cells with S. stercoralis L3s crude antigen (CA) and measured the expressions of genes related with antigen presentation and cytokine productions by quantitative real-time PCR; including MHC-II, CD40, CD80, TLR-2, TLR-4, IL-6, IL-10, TNF-α, and TGF-β. The results showed that the expression levels of MHC-II, CD40, CD80, TLR-2, TLR-4 after the stimulation by CA were not significantly different from negative controls. While the expression levels of IL-6 gene were not changed, TNF-α expression levels were significantly increased at 1 hr after CA treatment. Interestingly, the significant up-regulation of IL-10 and TGF-β expression of were detected in DC2.4 treated with CA. Luminex multiplex assays for detection of cytokine productions also showed significantly increased levels of IL-10 and TGF-β in the supernatant collected from DC2.4 treated with CA and excretory-secretory antigens (ES). Unfortunately, cofactor independent phosphoglycerate mutase (iPGM) antigen could not induced the IL-10 and TGF-β production from DC2.4. Like CA and ES antigens, iPGM could not induced the TNF-α and IL-6 production from DC2.4. Our results suggested that S. stercoralis modulates the host’s immune responses through induction of Treg response-related cytokines from DCs, including IL-10 and TGF-β. The antigens that play the crucial roles in regulation mechanism is excretory secretory products of S. stercoralis. The iPGM antigen might involve in the suppression of inflammatory responses, but not involved in the regulatory responses. The immunomodulation of the immune responses in the hosts should be complex and related to several antigens from the parasites. Nevertheless, S. stercoralis may have more than one evasion mechanism. Co-culturing between DCs and T cells will give more information about the immunomodulation of S. stercoralis and lead to the development of novel medical treatment for strongyloidiasis.