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

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/mm(3), 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.

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.

• Authors: 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 Jr
• Journal: PLoS neglected tropical diseases (PLoS Negl Trop Dis) Vol. 3 Issue 6 Pg. e456 (Jun 09 2009) ISSN: 1935-2735 [Electronic] United States
• PMID: 19513105 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Helminth
• CD4 Antigens
• FOXP3 protein, human
• Forkhead Transcription Factors
• IL5 protein, human
• Interleukin-2 Receptor alpha Subunit
• Interleukin-5

Topics

• Adult
• Aged
• Animals
• Antigens, Helminth (immunology)
• CD4 Antigens (analysis)
• Cells, Cultured
• Female
• Flow Cytometry
• Forkhead Transcription Factors (analysis)
• HTLV-I Infections (complications, immunology)
• Humans
• Interleukin-2 Receptor alpha Subunit (analysis)
• Interleukin-5 (immunology)
• Leukocytes, Mononuclear (immunology)
• Male
• Middle Aged
• Strongyloides stercoralis (immunology)
• Strongyloidiasis (complications, immunology)
• T-Lymphocyte Subsets (chemistry, immunology)
• T-Lymphocytes, Regulatory (immunology)
• Young Adult