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Infection and Immunity, April 2007, p. 1667-1678, Vol. 75, No. 4
0019-9567/07/$08.00+0     doi:10.1128/IAI.01156-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Echinococcus granulosus Antigen B Impairs Human Dendritic Cell Differentiation and Polarizes Immature Dendritic Cell Maturation towards a Th2 Cell Response{triangledown}

Rachele Riganò,1 Brigitta Buttari,1 Elisabetta Profumo,1 Elena Ortona,1 Federica Delunardo,1 Paola Margutti,1 Vincenzo Mattei,2,3 Antonella Teggi,4 Maurizio Sorice,2,3 and Alessandra Siracusano1*

Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Rome, Italy,1 Laboratorio di Medicina Sperimentale e Patologia Ambientale, Rieti, Università di Roma "La Sapienza," Rome, Italy,2 Dipartimento di Medicina Sperimentale e Patologia, Università di Roma "La Sapienza," Rome, Italy,3 Dipartimento di Malattie Infettive e Tropicali, Ospedale Sant'Andrea, Università di Roma "La Sapienza," Rome, Italy4

Received 24 July 2006/ Returned for modification 3 September 2006/ Accepted 2 January 2007

Despite inducing a strong host cellular and humoral immune response, the helminth Echinococcus granulosus is a highly successful parasite that develops, progresses, and ultimately causes chronic disease. Although surgery remains the preferred therapeutic option, pharmacological research now envisages antihelminthic strategies. To understand the mechanisms that E. granulosus uses to escape host immunosurveillance and promote chronic infection, we investigated how two hydatid cyst components, purified antigen B (AgB) and sheep hydatid fluid (SHF), act on host dendritic cell (DC) differentiation from monocyte precursors and how they influence maturation of DC that have already differentiated. We evaluated the immunomodulatory potential of these antigens by performing immunochemical and cytofluorimetric analyses of monocyte-derived DCs from healthy human donors. During monocyte differentiation, AgB and SHF downmodulated CD1a expression and upregulated CD86 expression. Compared with immature DCs differentiated in medium alone (iDCs), AgB- and SHF-differentiated cells stimulated with lipopolysaccharide included a significantly lower percentage of CD83+ cells (P < 10–4) and had weaker costimulatory molecule expression. When stimulated with AgB and SHF, iDCs matured and primed lymphocytes towards the Th2 response typical of E. granulosus infection. SHF and particularly AgB reduced the production of interleukin-12p70 (IL-12p70) and tumor necrosis factor alpha in lipopolysaccharide-stimulated iDCs. Anti-IL-10 antibodies increased the levels of IL-12p70 secretion in AgB- and SHF-matured DCs. AgB and SHF induced interleukin-1 receptor-associated kinase phosphorylation and activated nuclear factor-{kappa}B, suggesting that Toll-like receptors could participate in E. granulosus-stimulated DC maturation. These results suggest that E. granulosus escapes host immunosurveillance in two ways: by interfering with monocyte differentiation and by modulating DC maturation.

* Corresponding author. Mailing address: Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. Phone: 39 06 49 90 2760. Fax: 39 06 49 38 7112. E-mail: siracusano{at}iss.it.

{triangledown} Published ahead of print on 8 January 2007.

Editor: J. F. Urban, Jr.

Infection and Immunity, April 2007, p. 1667-1678, Vol. 75, No. 4
0019-9567/07/$08.00+0     doi:10.1128/IAI.01156-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zhang, W., Ross, A. G., McManus, D. P. (2008). Mechanisms of Immunity in Hydatid Disease: Implications for Vaccine Development. J. Immunol. 181: 6679-6685 [Abstract] [Full Text]  


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