TLR7/8 ligand, R-848, inhibits IgE synthesis by acting directly on B lymphocytes

TLRs are involved in the regulation of immune responses. R-848, a TLR7/8 ligand, has potent anti-viral and anti-tumour properties and has been used as a new immune response modifier for enhancing Th1 immune response. In this study, we found that R-848 significantly inhibited IgE synthesis from murine B cells at the single cell levels by anti-CD40 plus IL-4-stimulated splenocytes, in which R-848 acted on the early stage of B cell differentiation to modulate IgE synthesis. This inhibitory effect of R-848 on IgE synthesis was not isotype specific as it also inhibited IgG1 synthesis. Moreover, R-848 had no significant effect on the production of IgG2a by anti-CD40 plus IL-4-stimulated splenocytes. Further studies showed that R-848 markedly promoted murine B cell activation induced by anti-CD40 plus IL-4 by up-regulating the expression of B cell activation markers CD25, CD69 and co-stimulatory molecule CD80. In contrast, R-848 inhibited the proliferation and division of murine B cells in anti-CD40 plus IL-4-stimulated splenocytes. R-848 promoted the production of IFN-γ and IL-12 that were partially responsible for its inhibitory effect on IgE production by anti-CD40 plus IL-4 because the addition of anti-IFN-γ or anti-IL-12 mAbs to the cultures could significantly restore IgE production by splenocytes. Importantly, R-848 had a direct effect on purified B cells to inhibit IgE production induced by anti-CD40 plus IL-4. Taken together, these results demonstrate that R-848 markedly inhibits IgE synthesis, and suggest that R-848 could be used to treat allergic diseases. © 2008 The Authors.link_to_subscribed_fulltex

Wheat curl mite, Aceria tosichella, and transmitted viruses: an expanding pest complex affecting cereal crops

The wheat curl mite (WCM), Aceria tosichella, and the plant viruses it transmits represent an invasive mite-virus complex that has affected cereal crops worldwide. The main damage caused by WCM comes from its ability to transmit and spread multiple damaging viruses to cereal crops, with Wheat streak mosaic virus (WSMV) and Wheat mosaic virus (WMoV) being the most important. Although WCM and transmitted viruses have been of concern to cereal growers and researchers for at least six decades, they continue to represent a challenge. In older affected areas, for example in North America, this mite-virus complex still has significant economic impact. In Australia and South America, where this problem has only emerged in the last decade, it represents a new threat to winter cereal production. The difficulties encountered in making progress towards managing WCM and its transmitted viruses stem from the complexity of the pathosystem. The most effective methods for minimizing losses from WCM transmitted viruses in cereal crops have previously focused on cultural and plant resistance methods. This paper brings together information on biological and ecological aspects of WCM, including its taxonomic status, occurrence, host plant range, damage symptoms and economic impact. Information about the main viruses transmitted by WCM is also included and the epidemiological relationships involved in this vectored complex of viruses are also addressed. Management strategies that have been directed at this mite-virus complex are presented, including plant resistance, its history, difficulties and advances. Current research perspectives to address this invasive mite-virus complex and minimize cereal crop losses worldwide are also discussed.Instituto de Patología VegetalFil: Navia, Denise. Embrapa Recursos Genéticos e Biotecnologia; BrasilFil: Mendonça, Renata Santos de. Embrapa Recursos Genéticos e Biotecnologia; BrasilFil: Skoracka, Anna. Adam Mickiewicz University. Faculty of Biology. Institute of Environmental Biology. Department of Animal Taxonomy and Ecology; PoloniaFil: Szydło, Wiktoria. Adam Mickiewicz University. Faculty of Biology. Institute of Environmental Biology. Department of Animal Taxonomy and Ecology; PoloniaFil: Knihinicki, Danuta. Orange Agricultural Institute. Agricultural Scientific Collections Unit. NSW Department of Primary Industries; AustraliaFil: Hein, Gary L. University of Nebraska at Lincoln; Estados UnidosFil: Pereira, Paulo Roberto Valle da Silva. Embrapa Trigo; BrasilFil: Truol, Graciela Ana Maria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; ArgentinaFil: Lau, Douglas. Embrapa Trigo; Brasi