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Clinical Trial
. 2014 Nov 6;10(11):e1004469.
doi: 10.1371/journal.ppat.1004469. eCollection 2014 Nov.

Unravelling human trypanotolerance: IL8 is associated with infection control whereas IL10 and TNFα are associated with subsequent disease development

Affiliations
Clinical Trial

Unravelling human trypanotolerance: IL8 is associated with infection control whereas IL10 and TNFα are associated with subsequent disease development

Hamidou Ilboudo et al. PLoS Pathog. .

Abstract

In West Africa, Trypanosoma brucei gambiense, causing human African trypanosomiasis (HAT), is associated with a great diversity of infection outcomes. In addition to patients who can be diagnosed in the early hemolymphatic phase (stage 1) or meningoencephalitic phase (stage 2), a number of individuals can mount long-lasting specific serological responses while the results of microscopic investigations are negative (SERO TL+). Evidence is now increasing to indicate that these are asymptomatic subjects with low-grade parasitemia. The goal of our study was to investigate the type of immune response occurring in these "trypanotolerant" subjects. Cytokines levels were measured in healthy endemic controls (n = 40), stage 1 (n = 10), early stage 2 (n = 19), and late stage 2 patients (n = 23) and in a cohort of SERO TL+ individuals (n = 60) who were followed up for two years to assess the evolution of their parasitological and serological status. In contrast to HAT patients which T-cell responses appeared to be activated with increased levels of IL2, IL4, and IL10, SERO TL+ exhibited high levels of proinflammatory cytokines (IL6, IL8 and TNFα) and an almost absence of IL12p70. In SERO TL+, high levels of IL10 and low levels of TNFα were associated with an increased risk of developing HAT whereas high levels of IL8 predicted that serology would become negative. Further studies using high throughput technologies, hopefully will provide a more detailed view of the critical molecules or pathways underlying the trypanotolerant phenotype.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Plasmatic cytokine profiles in HAT patients, SERO TL+ subjects, and endemic controls.
Box plots of cytokine concentration are presented. Boxes represent the medians and interquartile ranges and whiskers represent 10th and 90th percentiles. Asterisks indicate significant differences over the control group: ****, p<0.0001; ***, p<0.001; **, p<0.01; *, p<0.05 (nonparametric Wilcoxon signed-rank test). Only cytokines with significant differences are shown. Group effectives: control (n = 40); HAT (n = 52); SERO TL+ (n = 60).
Figure 2
Figure 2. Principal component analysis of cytokine responses in HAT patients and SERO TL+.
A. Histogram of eigenvalues. The eigenvalues, which corresponds to the amount of variance accounted by each component, are presented for the first ten components. The two first components, which explain more than 50% of the total variance, are in black. B. First factorial plan (x-axis: first component, y-axis: second component). The plan composed by the two first axis or dimensions is represented. It corresponds to an approximation of the cloud of points by a 2-dimensional space. C. Absolute contribution of each cytokine to the variance of the second component.
Figure 3
Figure 3. Evolution of the serological and parasitological status in SERO TL+ subjects.
The progression of CATT end titers over time is presented for individuals who were confirmed as HAT patients during their follow-up (A.), plain circles indicate that trypanosomes were detected by microscopy in blood or cervical lymph nodes; individuals with decreasing CATT responses (B.) and individuals who maintained high serological responses to the CATT during the follow-up period (C.).
Figure 4
Figure 4. Box-plots of IL10, TNFα, and IL8 concentrations measured in the plasma of SERO TL+ subjects at study inclusion according to follow-up results.
SERO TL+/HAT: individuals confirmed as HAT patients (n = 12); SERO TL+/CATTneg individuals with decreasing CATT responses with end titers becoming <1/8 (n = 15); SERO TL+/CATT≥1/8: individuals maintaining elevated CATT responses with end titers ≥1/8 (n = 13). Significant differences in cytokine levels are indicated (**: 0.01
Figure 5
Figure 5. Cytokine profiles and infection outcomes in gambiense HAT.

References

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