Toll-like signaling pathway in the transcriptome of Littorina littorea.

The transcriptome of the caenogastropod mollusk Littorina littorea was scanned for the presence of sequences encoding Toll-like receptors (TLRs) and corresponding proteins involved in downstream TLR signaling pathway. In the transcriptomic snapshots of hemocytes and kidney tissues, 45 complete TLRs encoded by 35 genes were identified. Out of the 59 non-TLR molecules involved in a canonical TLR signaling pathway, 35 genes were classified as homologous and could be placed within the TLR-mediated MyD88-and MAPK-dependent circuitries. No reference vertebrate adapters TIRAP, TRIF and TRAM were identified in the transcriptome. The results of RNA-seq experiments with an immune challenge (rediae of the digenean Himasthla elongata) indicate that four TLRs (LlTLR1, 3, 5 and 8) and a set of upregulated genes involved in signal transduction (LlMyd88, LlTNFα, LlCASP8, LlFADD, LlNFKBIA (IkBα), LlIRAK1, LlSTAT1, LlMAPK14 (P38), LlMAP2K1 (MEK1/2), LlIRF3 and LlIRF5) may participate in the anti-digenean immune response of L. littorea.

Rational design of novel TLR4 ligands by in silico screening and their functional and structural characterization in vitro.

The purpose of this study was to identify new small molecules that possess activity on human toll-like receptor 4 associated with the myeloid differentiation protein 2 (hTLR4/MD2). Following current rational drug design principles, we firstly performed a ligand and structure based virtual screening of more than 130 000 compounds to discover until now unknown class of hTLR4/MD2 modulators that could be used as novel type of immunologic adjuvants. The core of the in silico study was molecular docking of flexible ligands in a partially flexible hTLR4/MD2 receptor model using a peta-flops-scale supercomputer. The most promising substances resulting from this study, related to anthracene-succimide hybrids, were synthesized and tested. The best prepared candidate exhibited 80% of Monophosphoryl Lipid A in vitro agonistic activity in cell lines expressing hTLR4/MD2.

Innate Immunity Provides Biomarkers of Health for Teleosts Exposed to Nanoparticles.

In recent years, the unique properties of nanoparticles have fostered novel applications in various fields such as biology, pharmaceuticals, agriculture, and others. Unfortunately, their rapid integration into daily life has also led to environmental concerns due to uncontrolled release of nanoparticles into the aquatic environment. Despite increasing awareness of nanoparticle bioaccumulation in the aquatic environment, much remains to be learned about their impact on aquatic organisms and how to best monitor these effects. Herein, we provide the first review of innate immunity as an emerging tool to assess the health of fish following nanoparticle exposure. Fish are widely used as sentinels for aquatic ecosystem pollution and innate immune parameters offer sensitive and reliable tools that can be harnessed for evaluation of contamination events. The most frequent biomarkers highlighted in literature to date include, but are not limited to, parameters associated with leukocyte dynamics, oxidative stress, and cytokine production. Taken together, innate immunity offers finite and sensitive biomarkers for assessment of the impact of nanoparticles on fish health.

Plant Pathogenesis-Related Proteins PR-10 and PR-14 as Components of Innate Immunity System and Ubiquitous Allergens.

Pathogenesis-related (PR) proteins are components of innate immunity system in plants. They play an important role in plant defense against pathogens. Lipid transfer proteins (LTPs) and Bet v 1 homologs comprise of two separate families of PR-proteins. Both LTPs (PR-14) and Bet v 1 homologs (PR-10) are multifunctional small proteins involving in plant response to abiotic and biotic stress conditions. The representatives of these PR-protein families do not show any sequence similarity but have other common biochemical features such as low molecular masses, the presence of hydrophobic cavities, ligand binding properties, and antimicrobial activities. Besides, many members of PR-10 and PR-14 families are ubiquitous plant panallergens which are able to cause sensitization of human immune system and crossreactive allergic reactions to plant food and pollen. This review is aimed at comparative analysis of structure-functional and allergenic properties of the PR-10 and PR-14 families, as well as prospects for their medicinal application.