Helminth-associated systemic immune activation and HIV co-receptor expression: response to albendazole/praziquantel treatment

PLoS Negl Trop Dis. 2014 Mar 27;8(3):e2755. doi: 10.1371/journal.pntd.0002755. eCollection 2014 Mar.

Abstract

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-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).

Conclusions: Increased expression of T cell activation markers was associated with Trichuris and Ascaris infections with relatively little effect of helminth treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Albendazole / therapeutic use*
  • Animals
  • Anthelmintics / therapeutic use
  • Antigens, CD / analysis
  • Cytokines / blood
  • Female
  • Flow Cytometry
  • Gene Expression
  • Gene Expression Profiling
  • HIV Infections / complications*
  • HLA-DR Antigens / analysis
  • Helminthiasis / complications*
  • Helminthiasis / drug therapy
  • Helminthiasis / immunology*
  • Helminths / immunology*
  • Humans
  • Male
  • Middle Aged
  • Praziquantel / therapeutic use*
  • Receptors, CCR5 / analysis
  • Receptors, HIV / biosynthesis*
  • Tanzania
  • Young Adult

Substances

  • Anthelmintics
  • Antigens, CD
  • CCR5 protein, human
  • Cytokines
  • HLA-DR Antigens
  • Receptors, CCR5
  • Receptors, HIV
  • Praziquantel
  • Albendazole

Grants and funding

The EMINI study was funded by the European Union (SANTE/2004/078-545 and SANTE/2006/129-931). The WHIS study was funded by the German Research Foundation (DFG, grant SA 1878/1-1) with additional support by the European Community's Seventh Framework Programme (FP7/2007–2013 and FP7/2007–2011 under EC-GA n° 241642). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.