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Prostaglandin E-2 is a major inhibitor of dendritic cell maturation and function in Ixodes scapularis saliva

  1. Author:
    Sa-Nunes, A.
    Bafica, A.
    Lucas, D. A.
    Conrads, T. P.
    Veenstra, T. D.
    Andersen, J. F.
    Mather, T. N.
    Ribeiro, J. M. C.
    Francischetti, I. M. B.

  2. Author Address

    NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Bethesda, MD 20892 USA. Univ Fed Santa Catarina, Div Immunol Microbiol, Florianopolis, SC, Brazil. Univ Fed Santa Catarina, Dept Parasitol, Florianopolis, SC, Brazil. Natl Canc Inst, SAIC Frederick, Lab Proteom & Analyt Technol, NIH, Frederick, MD 21702 USA. Univ Rhode Isl, Ctr Vector Borne Dis, Kingston, RI 02881 USA.;Francischetti, IMB, NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.;ifrancischetti@niaid.nih.gov
    1. Year: 2007
    2. Date: Aug
  2. Journal: Journal of Immunology
    1. 179
    2. 3
    3. Pages: 1497-1505
  4. Type of Article: Article
  5. ISSN: 0022-1767
  1. Abstract:

    Tick saliva is thought to contain a number of molecules that prevent host immune and inflammatory responses. In this study, the effects of Ixodes scapularis saliva on cytokine production by bone marrow-derived dendritic cells (DCs) from C57BL/6 mice stimulated by TLR-2, TLR-4, and TLR-9 ligands were studied. Saliva at remarkably diluted concentrations (< 1/2000) promotes a dose-dependent inhibition of IL-12 and TNF-alpha production induced by all TLR ligands used. Using a combination of fractionation techniques (microcon filtration, molecular sieving, and reversed-phase chromatography), we unambiguously identified PGE(2) as the salivary inhibitor of IL-12 and TNF-alpha production by DCs. Moreover, we have found that I. scapularis saliva (dilution 1/200; similar to 10 nM PGE(2)) marginally inhibited LPS-induced CD40, but not CD80, CD86, or MHC class II expression. In addition, saliva significantly suppressed the ability of DCs to stimulate Ag-specific CD4(+) T cell proliferation and IL-2 production. Notably, the effect of saliva on DC maturation and function was reproduced by comparable concentrations of standard PGE2. These findings indicate that PGE2 accounts for most inhibition of DC function observed with saliva in vitro. The role of salivary PGE2 in vector-host interaction and host immune modulation and inflammation in vivo is also discussed. This study is the first to identify molecularly a DC inhibitor from blood-sucking arthropods.

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External Sources

  1. View record in Web of Science®
  2. WOS: 000248319700012

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