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

Background: It 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. Objective: To study systemic immune activation and HIV-1 co-receptor expression in relation to different helminth infections and in response to helminth treatment. Methods: HIV-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. Results: Trichuris 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-1 beta 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). Conclusions: Increased expression of T cell activation markers was associated with Trichuris and Ascaris infections with relatively little effect of helminth treatment

Expression of systemic T cell activation markers in relation to infection with different helminth species.

<p>The frequencies of HLA-DR⁺CD38⁻ and total HLA-DR⁺ (B) are shown on the y-axis for CD4 (left panels) and CD8 T cells (right panels). The worm infection status is indicated on the x-axis stratified into worm negative individuals or those infected with TT (<i>Trichuris trichiura</i>), SH (<i>Schistosoma haematobium</i>), SM (<i>Schistosoma mansoni</i>), AL (<i>Ascaris lumbricoides</i>) or HW (Hookworm). Statistical analysis was performed using Mann-Whitney test for comparing groups. Shown in (C) is a linear regression analysis between the frequency of HLA-DR⁺/CD38⁺ CD8 T cells and the worm egg counts (as measured by Kato-Katz method) within Trichuris (left panel) and <i>S. mansoni</i> (right panel) infected subjects.</p

WHIS study cohort.

<p>WHIS study cohort.</p

Expression of activation markers on CD4 and CD8 T cells in relation to chronic infection with different helminth species on HIV negative individuals.

<p>*P values for comparison between helminth infected and non-infected controls were calculated using the Mann-Whitney test.</p