Immunosuppressive PAS-1 is an excretory/secretory protein released by larval and adult worms of the ascarid nematode Ascaris suum.
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.
Laboratory of Immunopathology, Butantan Institute,São Paulo,Brazil.
M F P
MF
Antunes
Laboratory of Immunopathology, Butantan Institute,São Paulo,Brazil.
T O
TO
Titz
Peptide and Protein Sequencing Unit, Butantan Institute,São Paulo,Brazil.
I F C
IF
Batista
Peptide and Protein Sequencing Unit, Butantan Institute,São Paulo,Brazil.
R
R
Marques-Porto
Laboratory of Immunopathology, Butantan Institute,São Paulo,Brazil.
C F
CF
Oliveira
Laboratory of Immunopathology, Butantan Institute,São Paulo,Brazil.
C A
CA
Alves de Araujo
Laboratory of Immunopathology, Butantan Institute,São Paulo,Brazil.
M F
MF
Macedo-Soares
D000818:Animals; D017165:Ascaris suum / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects; D003470:Culture Media / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015801:Helminth Proteins / Q000276:immunology* / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000378:metabolism*; D007814:Larva / Q000737:chemistry / Q000276:immunology / Q000502:physiology; D007962:Leukocytes / Q000378:metabolism / Q000502:physiology; D013997:Time Factors
D003470:Culture Media; D016207:Cytokines; D015801:Helminth Proteins; D007166:Immunosuppressive Agents; C511899:PAS-1 protein, Ascaris suum