Induction Of Il-10 And Tgf Beta From Cd4(+)Cd25(+)Foxp3(+) T Cells Correlates With Parasite Load In Indian Kala-Azar Patients Infected With Leishmania Donovani
PLOS NEGLECTED TROPICAL DISEASES(2016)
Abstract
BackgroundVisceral leishmaniasis (VL) is distinguished by a complex interplay of immune response and parasite multiplication inside host cells. However, the direct association between different immunological correlates and parasite numbers remains largely unknown.Methodology/Principal FindingsWe examined the plasma levels of different disease promoting/protective as well as Th17 cytokines and found IL-10, TGF beta and IL-17 to be significantly correlated with parasite load in VL patients (r = 0.52, 0.53 and 0.51 for IL-10, TGF beta and IL-17, respectively). We then extended our investigation to a more antigen-specific response and found leishmanial antigen stimulated levels of both IL-10 and TGF beta to be significantly associated with parasite load (r = 0.71 and 0.72 for IL-10 and TGF beta respectively). In addition to cytokines we also looked for different cellular subtypes that could contribute to cytokine secretion and parasite persistence. Our observations manifested an association between different Treg cell markers and disease progression as absolute numbers of CD4(+)CD25(+) (r = 0.55), CD4(+)CD25(hi) (r = 0.61) as well as percentages of CD4(+)CD25(+)FoxP3(+) T cells (r = 0.68) all correlated with parasite load. Encouraged by these results, we investigated a link between these immunological components and interestingly found both CD4(+)CD25(+) and CD4(+)CD25(+)FoxP3(+) Treg cells to secrete significantly (p < 0.05) higher amounts of not only IL-10 but also TGF beta in comparison to corresponding CD25-T cells.Conclusions/SignificanceOur findings shed some light on source(s) of TGF beta and suggest an association between these disease promoting cytokines and Treg cells with parasite load during active disease. Moreover, the direct evidence of CD4(+)CD25(+)FoxP3(+) Treg cells as a source of IL-10 and TGF beta during active VL could open new avenues for immunotherapy towards cure of this potentially fatal disease.
MoreTranslated text
Key words
Parasite Control
AI Read Science
Must-Reading Tree
Example
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
Generate MRT to find the research sequence of this paper
Chat Paper
Summary is being generated by the instructions you defined