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Mediation of T-Helper 17 Responses to Schistosomes by Dendritic Cells but Not Basophils

Meenu Sharma, Maxime Lecerf, Alain Friboulet, Srini V Kaveri, Colette Dissous,
Published in OXFORD UNIV PRESS INC
2015
Volume: 209
   
Issue: 12
Pages: 2019 - 2021
Abstract

T-helper (Th) 17 cells that express lineage-specific transcription factor RORC and produce cytokines interleukin 17A (IL-17A), interleukin 17F (IL-17F), and interleukin 22 (IL-22), play a key role in the clearance of both intracellular and extracellular bacteria and fungal infections. However, in the context of certain other infections, such as hepatitis B, chronic toxoplasmic uveitis, encephalitis, and Theiler murine encephalomyelitis, chronic activation of Th17 cells could contribute to tissue damage and immunopathology [1–3]. In line with these observations, Mbow et al [4] recently demonstrated that Th17 cells are associated with pathology in human schistosomiasis. They found elevated Th17 cells in peripheral blood of patients with schistosomiasis as well as in the liver and spleen of Schistosoma mansoni–infected mice. However, considering the essential role of innate immune cells in mediating T-cell responses, questions regarding the identification of innate cells that could promote Th17 responses during Schistosoma infection remain unexplored.

In this regard, dendritic cells (DCs) are innate immune cells extensively studied for their role in antigen presentation and in the regulation of T-cell responses to pathogens. However, there is also growing evidence to implicate basophils in eliciting immune responses against helminth parasites including schistosomes. Basophils were recruited rapidly to the lymph nodes after exposure to S. mansoni eggs [5]. Because both DCs and basophils have important roles in regulating immune responses to pathogens, we sought to explore which of the innate cells are implicated in driving Th17 responses to schistosomes, as reported by Mbow et al [4].

Dendritic cells were generated from peripheral blood monocytes, and basophils were isolated from peripheral blood mononuclear cells of healthy donors, as described elsewhere [6]. The S. mansoni eggs were obtained from 3–4 livers of golden hamsters infected with parasite cercarial larvae for 40 days [7]. The cell suspension was washed 3 times with Hank's balanced salt solution followed by collagenase B (100 µg/mL) treatment. The egg pellet was washed again with phosphate-buffered saline 3 times at 400 g for 1 minute. Eggs were counted, and the absence of contaminating hamster tissue fragments in the egg preparation was verified by microscopic analysis. CD4+ T cells were isolated from peripheral blood mononuclear cells by negative selection using a CD4+ T-cell isolation kit (Miltenyi Biotec). Regulatory T cells were removed by using CD25 microbeads (Miltenyi Biotec), and CD4+CD25− T cells were used for the experiments.

To investigate the differential effect of DCs and basophils to promote Th17 responses to schistosomes, either untreated or S. mansoni egg–treated DCs and basophils were cocultured with autologous CD4+CD25− T cells. After 4 days of culture, Th17 responses were analyzed by means of flow cytometry (BD LSR II) and measurement of Th17 cytokines in the cell-free culture supernatants.

About the journal
JournalThe Journal of Infectious Diseases
PublisherOXFORD UNIV PRESS INC
ISSN0022-1899
Open AccessNo