Helminth-Associated Systemic Immune Activation and HIV Co-receptor Expression: Response to Albendazole/Praziquantel Treatment

Mkunde Chachage,Elmar Saathoff,Onesmo Mgaya,Dickens Kowour,Leonard Maboko,Asli Bauer,Anthony Nsojo,Christof Geldmacher,Lilli Podola,Michael Hoelscher,Guenter Froeschl,Petra Clowes

doi:10.1371/journal.pntd.0002755

Abstract

BackgroundIt has been hypothesized that helminth infections increase HIV susceptibility by enhancing systemic immune activation and hence contribute to elevated HIV-1 transmission in sub-Saharan Africa.ObjectiveTo study systemic immune activation and HIV-1 co-receptor expression in relation to different helminth infections and in response to helminth treatment.MethodsHIV-negative adults with (n = 189) or without (n = 57) different helminth infections, as diagnosed by Kato-Katz, were enrolled in Mbeya, Tanzania. Blinded to helminth infection status, T cell differentiation (CD45RO, CD27), activation (HLA-DR, CD38) and CCR5 expression was determined at baseline and 3 months after Albendazole/Praziquantel treatment. Plasma cytokine levels were compared using a cytometric bead array.ResultsTrichuris and Ascaris infections were linked to increased frequencies of “activated” CD4 and/or CD8 T cells (p<0.05), whereas Hookworm infection was associated with a trend towards decreased HLA-DR+ CD8 T cell frequencies (p = 0.222). In Trichuris infected subjects, there was a linear correlation between HLA-DR+ CD4 T cell frequencies and the cytokines IL-1β and IL-10 (p<0.05). Helminth treatment with Albendazole and Praziquantel significantly decreased eosinophilia for S. mansoni and Hookworm infections (p<0.005) but not for Trichuris infection and only moderately modulated T cell activation. CCR5 surface density on memory CD4 T cells was increased by 1.2-fold during Trichuris infection (p-value: 0.053) and reduced after treatment (p = 0.003).ConclusionsIncreased expression of T cell activation markers was associated with Trichuris and Ascaris infections with relatively little effect of helminth treatment.

Highlights

In 1995, Bentwich et al proposed that systemic immune activation associated with chronic helminth infection may be the driving force of HIV transmission in Africa [1] as such infections are common in that environment
Increased expression of T cell activation markers was associated with Trichuris and Ascaris infections with relatively little effect of helminth treatment
Systemic T cell activation in subjects infected with different helminth species To examine whether different helminth infections modulate systemic immune activation, we first studied the baseline expression of the T cell activation markers HLA-DR and CD38 on total CD4 and CD8 T cells in HIV negative volunteers with (n = 189) and without helminth infection (n = 57), as determined by the Kato-Katz method

Summary

Introduction

In 1995, Bentwich et al proposed that systemic immune activation associated with chronic helminth infection may be the driving force of HIV transmission in Africa [1] as such infections are common in that environment (reviewed in [2]). Compared to Ethiopian migrants that had stayed in Israel for longer periods and had received standard anti-helminthic treatment upon arrival, HLADR expression on CD4 and CD8 T cells and lymphocyte apoptosis was substantially higher in the new arrivals [3]. Within a similar study population, the same group reported higher CCR5 and CXCR4 expression levels in Ethiopians, regardless of the length of their residence in Israel and of the time after anti-helminthic treatment [4]. It has been hypothesized that helminth infections increase HIV susceptibility by enhancing systemic immune activation and contribute to elevated HIV-1 transmission in sub-Saharan Africa

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Results

Conclusion