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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1290-1298. Prepublished online as a Blood First Edition Paper on June 9, 2008; DOI 10.1182/blood-2008-04-149856. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-04-149856v1 112/4/1290    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Semnani, R. T. Articles by Nutman, T. B. Search for Related Content PubMed PubMed Citation Articles by Semnani, R. T. Articles by Nutman, T. B. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Inhibition of TLR3 and TLR4 function and expression in human dendritic cells by helminth parasites Roshanak Tolouei Semnani1, Priyanka Goel Venugopal1, Cynthia A. Leifer2, Sven Mostböck3, Helen Sabzevari3, and Thomas B. Nutman1 1 Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Cancer Institute, National Institutes of Health, Bethesda, MD; 2 Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY; and 3 Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD Patent lymphatic filariasis is characterized by antigen-specific T-cell unresponsiveness with diminished IFN- and IL-2 production and defects in dendritic cell (DC) function. Because Toll-like receptors (TLRs) play an important role in pathogen recognition and TLR expression is diminished on B and T cells of filaria-infected individuals, we examined the effect of live microfilariae (mf) on expression and function of TLRs in human DCs. We show that mf-exposed monocyte-derived human DCs (mhDCs) demonstrate marked diminution of TLR3 and TLR4 mRNA expression compared with mf-unexposed mhDCs that translated into loss of function in response to appropriate TLR ligands. Exposure to mf significantly down-regulated production of IFN-, MIP-1, IL-12p70, and IL-1 following activation with poly I:C, and of IL-12p40 following activation with poly I:C or LPS. mRNA expression of MyD88, the adaptor molecule involved in TLR4 signaling, was significantly diminished in mhDCs after exposure to mf. Moreover, mf interfered with NF-B activation (particularly p65 and p50) following stimulation with poly I:C or LPS. These data suggest that mf interfere with mhDC function by altering TLR expression and interfering with both MyD88-dependent signaling and a pathway that ultimately diminishes NF-B activity. This down-regulated NF-B activity impairs mhDC-produced cytokines needed for full T-cell activation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. M. Hamilton, D. J. Dowling, C. E. Loscher, R. M. Morphew, P. M. Brophy, and S. M. O'Neill The Fasciola hepatica Tegumental Antigen Suppresses Dendritic Cell Maturation and Function Infect. Immun., June 1, 2009; 77(6): 2488 - 2498. [Abstract] [Full Text] [PDF] K. Brannstrom, M. E. Sellin, P. Holmfeldt, M. Brattsand, and M. Gullberg The Schistosoma mansoni Protein Sm16/SmSLP/SmSPO-1 Assembles into a Nine-Subunit Oligomer with Potential To Inhibit Toll-Like Receptor Signaling Infect. Immun., March 1, 2009; 77(3): 1144 - 1154. [Abstract] [Full Text] [PDF]

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