Human Monocytes/Macrophage Inflammatory Cytokine Changes Following in vivo and in vitro Schistomam manoni Infection

Abstract

Introduction

Epidemiological and animal studies indicate that helminth infections have positive effects due to their potential to protect against autoimmune diseases. Here, we aim to assess the effect of S. mansoni infection on immune modulation of human monocytes and their potential protection against autoimmune disease development both in vivo and in vitro.

Materials and Methods

Monocytes were isolated from helminth-infected Ethiopians (MHIE), and from Dutch healthy volunteers (MHV). The MHV were stimulated in vitro with S. mansoni soluble egg antigens (SEA) or soluble worm antigens (SWA). In addition, phenotypical changes were studied directly, as well as after culturing for 6 days in the presence of human serum to obtain macrophages. Q-PCR, flow cytometry, multiplex bead immunoassay, and live-cell imaging were employed during analysis.

Results

MHIE showed elevated transcripts of SOCS-1 and TNF-α compared to MHV. Similarly, MHV that were stimulated with SEA demonstrated enhanced levels of SOCS-1, IL-10, and IL-12 mRNA, compared to control MHV. Remarkably, the SEA-treated monocytes showed a much higher motility than control monocytes, a hallmark of a patrolling phenotype. Furthermore, in vitro cultured macrophages that were stimulated by SEA exhibited enhanced mRNA levels of SOCS-1, IL-10, TNF-α, IL-12 and TGF-β, compared to control macrophages.

Conclusion

Macrophages from MHIE as well as SEA-treated MHV show an intermediate activation phenotype with both pro-inflammatory and anti-inflammatory characteristics in vitro. The observed pro-inflammatory properties might reflect a recent response of the cells due to contact with a pathogen, whereas the anti-inflammatory properties might contribute to helminth-induced protection against inflammatory diseases. Large-scale study is recommended to consolidate the findings of the present study.

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Keywords:

• Schistosoma mansoni
• immune modulation
• monocytes
• macrophages

Acknowledgment

This research was supported by a grant from CIS (VU University Amsterdam, the Netherlands). We thank the MCBI Department (VU University Medical Centre, Amsterdam, the Netherlands), for their hospitality to let MW perform part of the experiments in Amsterdam, and Drs Irma van Die, Christine Dijkstra and Gijs Kooijfor their help and valuable advice during the cell biological experiments. We greatly acknowledge the study participants, the volunteer blood donors, the support provided by Aklilu Lemma Institute of Pathobiology (ALIPB), and Armauer Hansen Research Institute (AHRI) (Ethiopia).

Author Contributions

All authors contributed to data analysis, drafting and revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.