Immunosuppressive PAS-1 is an excretory/secretory protein released by larval and adult worms of the ascarid nematode Ascaris suum

J Helminthol. 2015 May;89(3):367-74. doi: 10.1017/S0022149X14000200. Epub 2014 Apr 7.

Abstract

Helminths use several strategies to evade and/or modify the host immune response, including suppression or inactivation of the host antigen-specific response. Several helminth immunomodulatory molecules have been identified. Our studies have focused on immunosuppression induced by the roundworm Ascaris suum and an A. suum-derived protein named protein 1 from A. suum (PAS-1). Here we assessed whether PAS-1 is an excretory/secretory (E/S) protein and whether it can suppress lipopolysaccharide-induced inflammation. Larvae from infective eggs were cultured in unsupplemented Dulbecco's modified Eagle medium (DMEM) for 2 weeks. PAS-1 was then measured in the culture supernatants and in adult A. suum body fluid at different time points by enzyme-linked immunosorbent assay (ELISA) with the monoclonal antibody MAIP-1. Secreted PAS-1 was detected in both larval culture supernatant and adult body fluid. It suppressed lipopolysaccharide (LPS)-induced leucocyte migration and pro-inflammatory cytokine production, and stimulated interleukin (IL)-10 secretion, indicating that larval and adult secreted PAS-1 suppresses inflammation in this model. Moreover, the anti-inflammatory activity of PAS-1 was abolished by treatment with MAIP-1, a PAS-1-specific monoclonal antibody, confirming the crucial role of PAS-1 in suppressing LPS-induced inflammation. These findings demonstrate that PAS-1 is an E/S protein with anti-inflammatory properties likely to be attributable to IL-10 production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascaris suum / chemistry
  • Ascaris suum / immunology
  • Ascaris suum / physiology*
  • Cell Movement / drug effects
  • Culture Media / chemistry
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Helminth Proteins / immunology*
  • Helminth Proteins / metabolism*
  • Host-Pathogen Interactions
  • Immune Tolerance*
  • Immunosuppressive Agents / metabolism*
  • Larva / chemistry
  • Larva / immunology
  • Larva / physiology
  • Leukocytes / metabolism
  • Leukocytes / physiology
  • Time Factors

Substances

  • Culture Media
  • Cytokines
  • Helminth Proteins
  • Immunosuppressive Agents
  • PAS-1 protein, Ascaris suum