Downregulation of MIP-1α/CCL3 with praziquantel treatment in Schistosoma haematobiumand HIV-1 co-infected individuals in a rural community in Zimbabwe

RBL Zinyama-Gutsire,E Gomo,AE Butterworth,P Kallestrup,T Mduluza,C Erikstrup,S Munyati,H Ullum

doi:10.1186/1471-2334-9-174

Abstract

BackgroundChemokines have been reported to play an important role in granulomatous inflammation during Schistosoma mansoni infection. However there is less information on their role in Schistosoma haematobium infection, or on the effect of concurrent HIV-1 infection, as a potential modifying influence.MethodsTo determine levels of MIP-1α/CCL3 chemokine in plasma of S. haematobium and HIV-1 co-infected and uninfected individuals in a rural black Zimbabwean community.A cohort was established of HIV-1 and schistosomiasis infection and co-infection comprising 379 participants. Outcome measures consisted of HIV-1 and schistosomiasis status and levels of MIP-1α/CCL3 in plasma at baseline and three months post treatment. An association was established between MIP-1α/CCL3 plasma levels with HIV-1 and S. haematobium infections.ResultsA total of 379 adults formed the established cohort comprising 76 (20%) men and 303 (80%) women. Mean age was 33.25, range 17 - 62 years. The median MIP-1α/CCL3 plasma concentration was significantly higher in S. haematobium infected compared with uninfected individuals (p = 0.029). In contrast, there was no difference in the median MIP-1α/CCL3 levels between HIV-1 positive and negative individuals (p = 0.631). MIP-1α/CCL3 concentration in plasma was significantly reduced at three months after treatment with praziquantel (p = 000).ConclusionThe results of our study show that the MIP-1α/CCL3 levels were positively associated with S. haematobium egg counts at baseline but not with HIV-1 infection status. MIP-1α/CCL3 levels were significantly reduced at three months post treatment with praziquantel. We therefore conclude that MIP-1α/CCL3 is produced during infection with S haematobium. S. haematobium infection is associated with increased MIP-1α/CCL3 levels in an egg intensity-dependent manner and treatment of S. haematobium is associated with a reduction in MIP-1α/CCL3.

Highlights

Chemokines have been reported to play an important role in granulomatous inflammation during Schistosoma mansoni infection
The results of our study show that the MIP-1α/CCL3 levels were positively associated with S. haematobium egg counts at baseline but not with Human immunodeficiency virus (HIV)-1 infection status
S. haematobium infection is associated with increased MIP-1α/CCL3 levels in an egg intensity-dependent manner and treatment of S. haematobium is associated with a reduction in MIP-1α/CCL3

Summary

Introduction

Chemokines have been reported to play an important role in granulomatous inflammation during Schistosoma mansoni infection. Infection with HIV induces immune activation with high levels of circulating cytokines, such as tumor necrosis factor-alpha (TNF-α) [11,12], interleukin (IL-6) [13,14], IL-10 [13,15,16], and some chemokines [14,15]. The cytokines TNF-α and IL-6, as well as the chemokines IL-8 and MIP-1α/CCL3 can activate and assist the translocation of the transcription factor nuclear factor (NF)-κB in monocytes or macrophages [17]. In uninfected cells, this leads to cell proliferation and differentiation. The anti-inflammatory cytokines IL-10 and TGF-β downregulate the pro-inflammatory cytokine TNF-α and MIP-1α/CCL3, thereby inhibits HIV replication in vitro in macrophages [17,18,19]

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