Regulatory T cell expansion in HTLV-1 and strongyloidiasis co-infection is associated with reduced IL-5 responses to Strongyloides stercoralis antigen

Martin Montes, Cesar Sanchez, Kristien Verdonck, Jordan E. Lake, Elsa Gonzalez, Giovanni Lopez, Angelica Terashima, Thomas Nolan, Dorothy E. Lewis, Eduardo Gotuzzo, A. Clinton White

Research output: Chapter in Book/Report/Conference proceedingChapter

68 Citations (Scopus)

Abstract

Background: Human 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. Objective: To measure peripheral blood T regulatory cells and Strongyloides stercoralis larval antigen-specific cytokine responses in strongyloidiasis patients with or without HTLV-1 co-infection. Methods: Peripheral 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. Results: Patients 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 coinfected 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. Conclusions: Regulatory 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.

Original languageEnglish (US)
Title of host publicationPLoS Neglected Tropical Diseases
Volume3
Edition6
DOIs
StatePublished - 2009

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Strongyloidiasis
Strongyloides stercoralis
Human T-lymphotropic virus 1
Interleukin-5
Regulatory T-Lymphocytes
Coinfection
Antigens
Strongyloides
Eosinophils
Blood Cells
Parasites
Deltaretrovirus Infections
Cell Count
Infection
Infection Control
Analysis of Variance
Flow Cytometry
Adrenal Cortex Hormones
Down-Regulation

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Montes, M., Sanchez, C., Verdonck, K., Lake, J. E., Gonzalez, E., Lopez, G., ... White, A. C. (2009). Regulatory T cell expansion in HTLV-1 and strongyloidiasis co-infection is associated with reduced IL-5 responses to Strongyloides stercoralis antigen. In PLoS Neglected Tropical Diseases (6 ed., Vol. 3). [e456] https://doi.org/10.1371/journal.pntd.0000456

Regulatory T cell expansion in HTLV-1 and strongyloidiasis co-infection is associated with reduced IL-5 responses to Strongyloides stercoralis antigen. / Montes, Martin; Sanchez, Cesar; Verdonck, Kristien; Lake, Jordan E.; Gonzalez, Elsa; Lopez, Giovanni; Terashima, Angelica; Nolan, Thomas; Lewis, Dorothy E.; Gotuzzo, Eduardo; White, A. Clinton.

PLoS Neglected Tropical Diseases. Vol. 3 6. ed. 2009. e456.

Research output: Chapter in Book/Report/Conference proceedingChapter

Montes, M, Sanchez, C, Verdonck, K, Lake, JE, Gonzalez, E, Lopez, G, Terashima, A, Nolan, T, Lewis, DE, Gotuzzo, E & White, AC 2009, Regulatory T cell expansion in HTLV-1 and strongyloidiasis co-infection is associated with reduced IL-5 responses to Strongyloides stercoralis antigen. in PLoS Neglected Tropical Diseases. 6 edn, vol. 3, e456. https://doi.org/10.1371/journal.pntd.0000456
Montes M, Sanchez C, Verdonck K, Lake JE, Gonzalez E, Lopez G et al. Regulatory T cell expansion in HTLV-1 and strongyloidiasis co-infection is associated with reduced IL-5 responses to Strongyloides stercoralis antigen. In PLoS Neglected Tropical Diseases. 6 ed. Vol. 3. 2009. e456 https://doi.org/10.1371/journal.pntd.0000456
Montes, Martin ; Sanchez, Cesar ; Verdonck, Kristien ; Lake, Jordan E. ; Gonzalez, Elsa ; Lopez, Giovanni ; Terashima, Angelica ; Nolan, Thomas ; Lewis, Dorothy E. ; Gotuzzo, Eduardo ; White, A. Clinton. / Regulatory T cell expansion in HTLV-1 and strongyloidiasis co-infection is associated with reduced IL-5 responses to Strongyloides stercoralis antigen. PLoS Neglected Tropical Diseases. Vol. 3 6. ed. 2009.
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AU - Lake, Jordan E.

AU - Gonzalez, Elsa

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N2 - Background: Human 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. Objective: To measure peripheral blood T regulatory cells and Strongyloides stercoralis larval antigen-specific cytokine responses in strongyloidiasis patients with or without HTLV-1 co-infection. Methods: Peripheral 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. Results: Patients 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 coinfected 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. Conclusions: Regulatory 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.

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