Regulatory T Cell Expansion in HTLV-1 and Strongyloidiasis Co-infection Is Associated with Reduced IL-5 Responses to Strongyloides stercoralis Antigen

Abstract

BackgroundHuman strongyloidiasis varies from a chronic but limited infection in normal hosts to hyperinfection in patients treated with corticosteroids or with HTLV-1 co-infection. Regulatory T cells dampen immune responses to infections. How human strongyloidiasis is controlled and how HTLV-1 infection affects this control are not clear. We hypothesize that HTLV-1 leads to dissemination of Strongyloides stercoralis infection by augmenting regulatory T cell numbers, which in turn down regulate the immune response to the parasite.ObjectiveTo measure peripheral blood T regulatory cells and Strongyloides stercoralis larval antigen-specific cytokine responses in strongyloidiasis patients with or without HTLV-1 co-infection.MethodsPeripheral blood mononuclear cells (PBMCs) were isolated from newly diagnosed strongyloidiasis patients with or without HTLV-1 co-infection. Regulatory T cells were characterized by flow cytometry using intracellular staining for CD4, CD25 and FoxP3. PBMCs were also cultured with and without Strongyloides larval antigens. Supernatants were analyzed for IL-5 production.ResultsPatients with HTLV-1 and Strongyloides co-infection had higher parasite burdens. Eosinophil counts were decreased in the HTLV-1 and Strongyloides co-infected subjects compared to strongyloidiasis-only patients (70.0 vs. 502.5 cells/mm3, p = 0.09, Mann-Whitney test). The proportion of regulatory T cells was increased in HTLV-1 positive subjects co-infected with strongyloidiasis compared to patients with only strongyloidiasis or asymptomatic HTLV-1 carriers (median = 17.9% vs. 4.3% vs. 5.9 p<0.05, One-way ANOVA). Strongyloides antigen-specific IL-5 responses were reduced in strongyloidiasis/HTLV-1 co-infected patients (5.0 vs. 187.5 pg/ml, p = 0.03, Mann-Whitney test). Reduced IL-5 responses and eosinophil counts were inversely correlated to the number of CD4+CD25+FoxP3+ cells.ConclusionsRegulatory T cell counts are increased in patients with HTLV-1 and Strongyloides stercoralis co-infection and correlate with both low circulating eosinophil counts and reduced antigen-driven IL-5 production. These findings suggest a role for regulatory T cells in susceptibility to Strongyloides hyperinfection.

Strongyloides ratti Infection Induces Expansion of Foxp3+ Regulatory T Cells That Interfere with Immune Response and Parasite Clearance in BALB/c Mice

“…Montes et al (53) showed that an increased frequency of CD25 + Foxp3 + Tregs in the peripheral blood of human T cell-lymphotropic virus 1/Strongyloides-coinfected individuals resulted in increased worm burden and reciprocally decreased Teff and CD4 + Foxp3 + Treg populations in naive mice or mice that had been infected for 2, 7, or 14 d. Combined results of two independent experiments (mean 6 SEM; n = 9). *p , 0.05, **p , 0.01 compared with naive control group; Student t test.…”

Dexamethasone Effects in the Strongyloides venezuelensis Infection in A Murine Model

“…may occur and can be potentially fatal, particularly in immunosupressed patients. 2 Clinically relevant immunosuppression in this context includes those with human T-lymphotropic virus type (HTLV)-1 infection, 3 organ transplant recipients, 4 patients treated with corticosteroids, [5][6][7] and malnourished individuals. 8 Dexamethasone (Dexa) has potent immunosuppressive actions and is used to dampen inflammatory responses, particularly in the setting of autoimmune diseases, organ transplantation, and chronic airway inflammatory conditions.…”

Clinical conditions associated withintestinal strongyloidiasis in Rio de Janeiro, Brazil

“…This association has been reported in Brazil by Furtado et al (17) . The synergistic effects of co-infection with HTLV and S. stercoralis, which have been demonstrated, suggest that co-infected patients exhibit elevated parasite burdens and HTLV-1 proviral loads (18) (19) (20) . With respect to the interaction between strongyloidiasis and acquired immunodefi ciency syndrome (AIDS), our study indicated that the frequency of HIV infection tended to be higher among S. stercoralis-positive patients than among S. stercoralisnegative patients but that this difference was not statistically signifi cant.…”