Additional file 1: Figure S1. of Toll-like receptor 2 (TLR2) plays a role in controlling cutaneous leishmaniasis in vivo, but does not require activation by parasite lipophosphoglycan

Lesion development in WT and TLR−/− mice upon infection with L. major after 18 weeks. WT, TLR2−/−, TLR1−/−, TLR6−/− and TLR4−/− mice (n = 4–5) were infected with 105 L. major promastigotes subcutaneously. Mice were monitored every week for the appearance and size of lesions. The mean lesion size (mm2) + SEM for each genotype is shown at each weekly time point post-infection up to the end of the experiment at 18 weeks. Knockout stains were compared to WT mice using the Mann-Whitney U test, where P < 0.05 was considered to indicate significant (*) differences. (TIF 28 kb

TLR9 Activation Is Triggered by the Excess of Stimulatory versus Inhibitory Motifs Present in Trypanosomatidae DNA

International audienceDNA sequences purified from distinct organisms, e.g. non vertebrate versus vertebrate ones, were shown to differ in their TLR9 signalling properties especially when either mouse bone marrow-derived-or human dendritic cells (DCs) are probed as target cells. Here we found that the DC-targeting immunostimulatory property of Leishmania major DNA is shared by other Trypanosomatidae DNA, suggesting that this is a general trait of these eukaryotic single-celled parasites. We first documented, in vitro, that the low level of immunostimulatory activity by vertebrate DNA is not due to its limited access to DCs' TLR9. In addition, vertebrate DNA inhibits the activation induced by the parasite DNA. This inhibition could result from the presence of competing elements for TLR9 activation and suggests that DNA from different species can be discriminated by mouse and human DCs. Second, using computational analysis of genomic DNA sequences, it was possible to detect the presence of over-represented inhibitory and under-represented stimulatory sequences in the vertebrate genomes, whereas L. major genome displays the opposite trend. Interestingly, this contrasting features between L. major and vertebrate genomes in the frequency of these motifs are shared by other Trypanosomatidae genomes (Trypanosoma cruzi, brucei and vivax). We also addressed the possibility that proteins expressed in DCs could interact with DNA and promote TLR9 activation. We found that TLR9 is specifically activated with L. major HMGB1-bound DNA and that HMGB1 preferentially binds to L. major compared to mouse DNA. Our results highlight that both DNA sequence and vertebrate DNA-binding proteins, such as the mouse HMGB1, allow the TLR9-signaling to be initiated and achieved by Trypanosomatidae DNA

The Genome of Botrytis cinerea, a Ubiquitous Broad Host Range Necrotroph

Botrytis cinerea is a necrotrophic ascomycete, causing serious pre- and postharvest crop losses worldwide on a wide variety of plant species. Considerable research in recent years has unraveled a variety of molecular tools that enables the fungus to invade host tissue, including the secretion of toxic proteins and metabolites and host cell wall degrading enzymes. High-quality sequences from two strains of B. cinerea revealed an average-sized genome with a low fraction of repetitive DNA and no specific features correlated with its pathogenic lifestyle, except for a large number of genes encoding pectin-degrading enzymes that are particularly active on cell walls of dicot hosts. The genome sequences enabled genomics, transcriptomics, proteomics, and map-based cloning approaches that have resulted in the identification of genes important for the regulation of secondary metabolite synthesis, drug efflux, light-dependent processes, and pathogenicity. The recent availability of more genome sequences from different B. cinerea strains and Botrytis species and the combination of different ‘omics’ approaches will rapidly increase our understanding of the biology and diverse infection strategies of the gray mold fungus