Schistosoma mansoni soluble egg antigen (SEA) and recombinant Omega-1 modulate induced CD4+ T-lymphocyte responses and HIV-1 infection in vitro

PLoS Pathog. 2019 Sep 5;15(9):e1007924. doi: 10.1371/journal.ppat.1007924. eCollection 2019 Sep.

Abstract

Parasitic helminths evade, skew and dampen human immune responses through numerous mechanisms. Such effects will likely have consequences for HIV-1 transmission and disease progression. Here we analyzed the effects that soluble egg antigen (SEA) from Schistosoma mansoni had on modulating HIV-1 infection and cytokine/chemokine production in vitro. We determined that SEA, specifically through kappa-5, can potently bind to DC-SIGN and thereby blocks DC-SIGN mediated HIV-1 trans-infection (p<0.05) whilst not interfering with cis-infection. DCs exposed to SEA whilst maturing under Th2 promoting conditions, will upon co-culture with naïve T-cells induce a T-cell population that was less susceptible to HIV-1 R5 infection (p<0.05) compared to DCs unexposed to SEA, whereas HIV-1 X4 virus infection was unaffected. This was not observed for DCs exposed to SEA while maturing under Th1 or Th1/Th2 (Tmix) promoting conditions. All T-cell populations induced by SEA exposed DCs demonstrate a reduced capacity to produce IFN-γ and MIP-1β. The infection profile of T-cells infected with HIV-1 R5 was not associated with down-modulation of CCR5 cell surface expression. We further show that DCs maturing under Tmix conditions exposed to plant recombinant omega-1 protein (rω-1), which demonstrates similar functions to natural ω-1, induced T-cell populations that were less sensitive for HIV-1 R5 infection (p<0.05), but not for X4 virus infection. This inhibition associated again with a reduction in IFN-γ and MIP-1β expression, but additionally correlated with reduced CCR5 expression. We have shown that SEA parasite antigens and more specifically rω-1 can modulate HIV-1 infectivity with the potential to influence disease course in co-infected individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Helminth / immunology*
  • Antibodies, Helminth / metabolism
  • Antigens, Helminth / immunology*
  • Antigens, Helminth / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Egg Proteins / immunology*
  • Egg Proteins / metabolism
  • HIV Infections / immunology
  • HIV Infections / metabolism*
  • HIV Infections / prevention & control
  • HIV-1 / immunology
  • Humans
  • Lymphocyte Activation
  • Receptors, CCR5 / metabolism
  • Schistosoma mansoni / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology
  • Virus Replication / immunology

Substances

  • Antibodies, Helminth
  • Antigens, Helminth
  • Cytokines
  • Egg Proteins
  • Receptors, CCR5
  • omega-1 antigen, Schistosoma mansoni

Grant support

This work was supported by European Community’s Seventh Framework Programme Grant 41642 (IDEA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.