Screening of an Echinococcus granulosus cDNA library with IgG4 from patients with cystic echinococcosis identifies a new tegumental protein involved in the immune escape

Author:

Ortona E1,Margutti P1,Delunardo F1,Nobili V1,Profumo E1,Riganò R1,Buttari B1,Carulli G2,Azzarà A2,Teggi A3,Bruschi F4,Siracusano A1

Affiliation:

1. Division of Immune-mediated Diseases, Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Italy

2. Division of Haematology, Department of Oncology, Transplants and New Technologies in Medicine, University of Pisa, Italy

3. Department of Infectious and Tropical Diseases, Sant’Andrea Hospital, University of Rome ‘La Sapienza’, Rome, Italy

4. Department of Experimental Pathology, M.B.I., University of Pisa, Pisa, Italy

Abstract

Summary The worldwide problem of chronic Echinococcus granulosus disease calls for new parasite-derived immunomodulatory molecules. By screening an E. granulosus cDNA library with IgG4 from patients with active cystic echinococcosis, we identified a cDNA that encodes a predicted partial protein that immunofluorescence studies localized in the protoscolex tegument and on the germinal layer of cyst wall. We named this protein EgTeg because the 105 amino acid sequence scored highest against a family of Schistosoma tegumental proteins. Evaluating the role of EgTeg in the human early inflammatory response we found that EgTeg significantly inhibited polymorphonuclear cell (PMN) chemotaxis. Cytometric analysis of intracellular cytokines disclosed a significantly higher percentage of cells producing IL-4 than IFN-γ (P = 0·001, Student's t-test) in T lymphocytes from patients with cystic echinococcosis stimulated with EgTeg. EgTeg induced weak Th1-dependent proliferation in 42% of patients’ peripheral blood mononuclear cells. In immunoblotting (IB) analysis of total IgG and IgG subclass responses to EgTeg in patients with cystic echinococcosis, patients with other parasitoses, patients with cystic lesions and healthy controls, total IgG specific to EgTeg yielded high sensitivity (73%) but low specificity (44%) precluding its use in immunodiagnosis. Conversely, IgG4 specific to EgTeg gave acceptable sensitivity (65%) and high specificity (89%) suggesting its use in immunodiagnosis to confirm ultrasound documented cysts suggestive of E. granulosus. Because the new tegumental antigen EgTeg inhibits chemotaxis, induces IL-4-positive T lymphocytes and noncomplement fixing antibodies (IgG4) it is an immunomodulatory molecule associated with chronic infection.

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

Reference49 articles.

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