Containment of aerogenic Mycobacterium tuberculosis infection in mice does not require MyD88 adaptor function for TLR2, -4 and -9.

The role of Toll-like receptors (TLR) and MyD88 for immune responses to Mycobacterium tuberculosis (Mtb) infection remains controversial. To address the impact of TLR-mediated pathogen recognition and MyD88-dependent signaling events on anti-mycobacterial host responses, we analyzed the outcome of Mtb infection in TLR2/4/9 triple- and MyD88-deficient mice. After aerosol infection, both TLR2/4/9-deficient and wild-type mice expressed pro-inflammatory cytokines promoting antigen-specific T cells and the production of IFN-gamma to similar extents. Moreover, TLR2/4/9-deficient mice expressed IFN-gamma-dependent inducible nitric oxide synthase and LRG-47 in infected lungs. MyD88-deficient mice expressed pro-inflammatory cytokines and were shown to expand IFN-gamma-producing antigen-specific T cells, albeit in a delayed fashion. Only mice that were deficient for MyD88 rapidly succumbed to unrestrained mycobacterial growth, whereas TLR2/4/9-deficient mice controlled Mtb replication. IFN-gamma-dependent restriction of mycobacterial growth was severely impaired only in Mtb-infected MyD88, but not in TLR2/4/9-deficient bone marrow-derived macrophages. Our results demonstrate that after Mtb infection neither TLR2, -4, and -9, nor MyD88 are required for the induction of adaptive T cell responses. Rather, MyD88, but not TLR2, TLR4 and TLR9, is critical for triggering macrophage effector mechanisms central to anti-mycobacterial defense

The equine alveolar macrophage:functional and phenotypic comparisons with peritoneal macrophages

Alveolar macrophages (AMs) constitute the first line of defence in the lung of all species, playing a crucial role in the regulation of immune responses to inhaled pathogens. A detailed understanding of the function and phenotype of AMs is a necessary pre-requisite to both elucidating their role in preventing opportunistic bacterial colonisation of the lower respiratory tract and developing appropriate preventative strategies. The purpose of the study was to characterise this important innate immune cell at the tissue level by making functional and phenotypic comparisons with peritoneal macrophages (PMs). We hypothesised that the tissue of origin determines a unique phenotype of AMs, which may constitute an appropriate therapeutic target for certain equine respiratory diseases. Macrophages isolated from the lung and the peritoneal cavity of 9 horses were stimulated with various toll like receptor (TLR) ligands and the production of nitrite, tumour necrosis factor alpha (TNFα), interleukin (IL) 10 and indoleamine 2,3-dioxygenase (IDO) were measured by the Griess reaction and enzyme linked immunosorbent assay (ELISA) and/or quantitative polymerase chain reaction, respectively. Cells were also compared on the basis of phagocytic-capacity and the expression of several cell surface markers. AMs, but not PMs, demonstrated increased TNFα release following stimulation with LPS, polyinosinic polycytidylic acid (Poly IC) and heat-killed Salmonella typhinurium and increased TNFα and IDO mRNA expression when stimulated with LPS. AMs showed high expression of the specific macrophage markers cluster of differentiation (CD) 14, CD163 and TLR4, whereas PMs showed high expression of TLR4 only. AMs, but not PMs, demonstrated efficient phagocytic activity. Our results demonstrate that AMs are more active than PMs when stimulated with various pro-inflammatory ligands, thus supporting the importance of the local microenvironment in the activation status of the macrophage. This information provides a valuable knowledge base on which to improve our understanding of the role of macrophages and their microenvironment in equine innate immunity

Circulating microparticles: square the circle

Background: The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results: MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions: Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes

Alterações oftalmológicas em pacientes com COVID-19: revisão narrativa de estudos e séries de casos

O objetivo deste trabalho é descrever casos clínicos e séries de casos relacionados a alterações oftalmológicas em pacientes com diagnóstico de COVID-19. Foi realizada uma revisão narrativa/descritiva de casos clínicos e série de casos. A partir das buscas de dados com descritores pré-definidos, foram integrados na revisão, 17 estudos. Dentre os principais temas identificados, destacam-se: alterações conjuntivais, alterações retinianas e oftalmoparesias. O quadro de alterações da conjuntiva foi prevalente em relação aos demais. Essa revisão incluiu não apenas afecções oculares em adultos, mas também, em crianças e adolescentes. O estudo chama atenção para o fato de que as alterações oculares foram descritas como alteração isolada, alteração precipitante e alteração simultânea ao quadro respiratório. Conclui-se que as afecções oculares vão além de alterações conjuntivais, embora sejam essas preponderantes, havendo ainda alterações retinianas, quadro de oftalmoparesia e ainda a incomum síndrome de Miller Fisher. Novos ensaios irão poder avaliar, qual é de fato, a representatividade dos problemas oculares na cadeia epidemiológica da COVID-19.The objective of this work is to describe clinical cases and case series related to ophthalmological changes in patients diagnosed with COVID-19. A narrative/descriptive review of clinical cases and case series was performed. Based on data searches with pre-defined descriptors, 17 studies were integrated in the review. Among the main themes identified, the following stand out: conjunctival changes, retinal changes and ophthalmoparesis. The picture of changes in the conjunctiva was prevalent in relation to the others. This review included not only eye disorders in adults, but also in children and adolescents. The study draws attention to the fact that the ocular changes were described as isolated alteration, precipitating alteration and simultaneous alteration to the respiratory condition. It is concluded that ocular conditions go beyond conjunctival alterations, although these are predominant, with retinal alterations, ophthalmoparesis and the unusual Miller Fisher syndrome. New trials will be able to assess, in fact, the representativeness of eye problems in the epidemiological chain of COVID-19

Diversity arrays technology (DArT) and statistical tools for genome profile-based molecular breeding of sugarcane : [Abstract W305]

Diversity Arrays Technology (DArT) combines the ability to identify various types of DNA polymorphism with the low cost and high throughput platforms DArT offers several-fold gain over other technologies in terms of marker throughput and assay cost and was successfully deployed in over 50 organisms including those with complex, polyploid genomes (www.DiversityArrays.com). We will report the current status of technology development of DArT for sugarcane, one of the most genetically complex crops. Several effective methods of genome complexity reduction were established leading to creation of genotyping array containing 7.680 probes. All markers on the array were sequenced. The analysis of sequence data shows that similarly to other crops sugarcane DArT markers are highly enriched for the genic, low copy number, sequences, enabling effective comparison against sorghum genome assembly. The genotyping array was successfully used for diversity analysis of cultivated materials and ancestral lines as well as for genetic mapping in several populations. The good genome coverage afforded by DArT array enabled efficient discovery of significant marker-trait associations and informed decisions on initiating molecular breeding of sugarcane in Australia. Several challenges identified in the course of technology development and application as well as some novel approaches to dealing with molecular marker and phenotypic data will be presented. (Texte intégral

Characterisation of psoriasis susceptibility locus 6 (PSORS6) in patients with early onset psoriasis and evidence for interaction with PSORS1

International audiencePsoriasis is a genetically complex, chronic inflammatory skin disease. We have previously identified a susceptibility locus on chromosome 19p13 (PSORS6). In a follow-up linkage disequilibrium (LD) study in an independent family based cohort, we found evidence for association to a newly discovered microsatellite at this locus (D19SPS21, p < 5.3*10-5). An LD-based association scan in 300 trios revealed association to several single SNPs in one LD block. When we stratified this cohort for carrying the PSORS1 risk allele at the HLA-C locus, evidence for association became much stronger at single SNP and haplotype levels (p-values between 1.0*10-4 and 8.0*10-4). In a replication study of 1,114 patients and 937 control individuals, evidence for association was also observed after stratification to the PSORS1 risk allele. In both study groups, logistic regression showed evidence for interaction between the risk alleles at PSORS1 and PSORS6. Best p-values for rs12459358 in both study groups remained significant after correction for multiple testing. The associated LD block did not comprise any known genes. Interestingly, an adjacent gene, MUC16, coding for a large glycosylated protein expressed in epithelia and of unknown function, could be shown to be also expressed in tissues relevant for pathogenesis of psoriasis such as skin and thymus. Immunohistochemical analyses of skin revealed focal staining for MUC16 in suprabasal epidermal cells. Further functional studies are required to clarify its potential role in psoriasis and identify the causal variant(s) at this locus. Our data establish PSORS6 as a confirmed psoriasis susceptibility locus showing interaction with PSORS1