Mannose-binding lectin (MBL) is a soluble lectin of the innate immune system that is produced by the liver and secreted into the circulation where it activates the lectin complement pathway, enhances phagocytosis of microorganisms by leukocytes, and modulates inflammation. MBL can recognize patterns on the surface of different pathogens, including Candida albicans. Our aims were to investigate whether MBL is expressed in the gut epithelium and to examine its effect on the modulation of intestinal inflammation and C. albicans elimination. Using reverse transcriptase-PCR, MBL transcripts were highly expressed in different parts of the mouse gut. MBL expression was also detected by immunoblotting and immunolocalization in response to C. albicans colonization of the gut; the highest expression of MBL was detected in the stomach. Blocking MBL by administering mannans to mice increased C. albicans colonization. MBL-deficient mice had a higher level of colonization than wild-type mice. Dextran sodium sulfate-induced colitis promoted C. albicans dissemination to the kidneys and lungs of MBL-deficient mice. MBL-deficient mice exhibited elevated expression of interleukin (IL)-17, IL-23, dectin-1, and Toll-like receptor-4. This study shows that MBL expression is induced in the gut in response to C. albicans sensing and is required for intestinal homeostasis and host defense against C. albicans.

Background Toll-like receptors (TLRs) are the major pattern recognition receptors that mediate sensing of a wide range of microorganisms. TLR2 forms heterodimers with either TLR1 or TLR6, broadening its ligand diversity against pathogens. TLR1, TLR2 and TLR6 have been implicated in the recognition of Candida albicans, an opportunistic fungal pathogen that colonizes the gastrointestinal tract. In this study, we explored whether the deficiency in TLR1, TLR2 or TLR6 impacts C. albicans colonization and inflammation-associated colonic injury in the dextran sulfate sodium (DSS)-induced colitis in mice.ResultsDSS treatment and C. albicans challenge induced greater weight loss, worse clinical signs of inflammation, higher histopathologic scores, and increased mortality rates in TLR1−/− and TLR2−/− mice when compared to TLR6−/− and wild-type mice. The number of C. albicans colonies in the stomach, colon and feces was decreased in TLR6−/− mice as compared to TLR2−/−, TLR1−/− and wild-type mice. Interestingly, the population of E. coli in colonic luminal contents, intestinal permeability to FITC-dextran and cytokine expression were significantly increased in TLR1−/− and TLR2−/− mice, while they were decreased in TLR6−/− mice.ConclusionIn contrast to TLR6, both TLR1 and TLR2 deficiencies increased intestinal inflammation, and the overgrowth of C. albicans and E. coli populations in the colitis model, suggesting the involvement of TLR1 and TLR2 in epithelial homeostasis, and a role of TLR6 in increasing intestinal inflammation in response to pathogen-sensing.Electronic supplementary materialThe online version of this article (doi:10.1186/s13099-017-0158-0) contains supplementary material, which is available to authorized users.

Platelets are capable of binding, aggregating, and internalizing microorganisms, which enhances the elimination of pathogens from the blood. The yeast Candida albicans is a pathobiont causing life-threatening invasive infections. Its cell wall contains ␤-1,3 glucans that are known to trigger a wide range of host cell activities and to circulate during infection. We studied the effect of ␤-1,3 glucan fractions (BGFs) consisting of diglucosides (Glc2), tetraglucosides (Glc4), and pentaglucosides (Glc5) on human platelets, their mechanisms of action, and their possible impact on host defenses. The effect of BGFs on the coagulation process was determined by measuring thrombin generation. Platelets pretreated with BGFs were analyzed in terms of activation, receptor expression, aggregation, and adhesion to neutrophils and to C. albicans. The results show that BGFs affected the endogenous thrombin potential in a concentration-dependent manner. For platelet activation, BGFs at a low concentration (2 mol/l) reduced ATP release and prevented the phosphorylation of protein kinase C. BGFs diminished the expression of P-selectin and the activation of ␣ IIb␤3. BGFs decreased platelet aggregation and the interaction between thrombin-stimulated platelets and neutrophils, fibrinogen, and C. albicans. GLc5 decreased ATP release and TGF-␤1 production in response to TLR4 upregulation in thrombin-stimulated platelets, but TLR4 blockage abolished the effect of BGFs on platelets. This study provides evidence that fungal pentaglucosides modulate platelet activity mediated via TLR4 stimulation and reduce platelet-neutrophil interaction.

Interestingly, viruses have been reported to be associated with T1D occurrence in animals. Experimental animal models, as BioBreeding (BB)-rat, nonobese diabetic (NOD) mouse or specific transgenic mouse strains, were used to investigate the mechanism by which viruses can modulate diabetogenesis. Viruses and human type 1 diabetes RubellaSeveral reports have shown that congenital rubella was associated with induction of islet autoantibodies in 10% to 20% of cases of congenital rubella, within 5 to 25 years [18,56,71].

Mannose-binding lectin, together with mannose-associated serine proteases, activates the lectin pathway of the complement system and subsequent inflammatory mechanisms. An association between mannose-binding lectin deficiency and anti-Saccharomyces cerevisiae antibody levels is observed in Crohn’s disease and this deficiency is frequently associated with a severe Crohn’s disease phenotype. In the present study, we assessed the relationship between serum concentrations of mannose-binding lectin, mannose-binding lectin functional activity, MBL2 and NOD2 polymorphisms, anti-S. cerevisiae antibody levels and clinical Crohn’s disease phenotype in 69 Crohn’s disease patients and 30 age- and sex-matched healthy controls. The results show that the MBL2 variant rs5030737 at codon 52 was associated with a low level of mannose-binding lectin and impaired mannose-binding lectin–mannose-associated serine protease (MBL-MASP) functional activity in Crohn’s disease patients. This MBL2 variant was also associated with a higher level of anti-S. cerevisiae antibodies. In addition, the NOD2 variant rs2066844, which is associated with susceptibility to Crohn’s disease, was significantly correlated with an impairment in MBL-MASP functional activity. These results provide evidence that Crohn’s disease patients have an impairment in MBL-MASP functional activity and that this defect is associated with MBL2 and NOD2 variants.

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The link between personality and the interest of individuals for science has not been thoroughly explored. In this report, we studied psychopathological traits in students studying science in French top-ranking institutions. Three hundred and forty seven individuals answered questionnaires assessing autistic and schizotypal dimensions, as well as anxiety, depression symptomatology and attachment quality. A cluster analysis based on autistic and schizotypal traits led to the identification of 4 distinct profiles: a "low trait cluster", a "moderate autistic trait cluster", a "moderate schizotypal trait cluster" and a "high trait cluster" (HTC) composed of individuals with high scores on both autistic and schizotypal scales. Each cluster represented 20.1-27.1% of participants and was clearly different from the three others, both on autistic and on schizotypal dimensions. These groups could be also typified by their level of anxiety, depression or degraded attachment, which are proportional to the extent of psychopathological traits. Moreover, students from the HTC cluster displayed lower academic results, thus implying that autistic traits might impair success in science when they are associated with moderate schizotypal personality features. This study also suggests that depression and anxiety might mediate performance inhibition in the HTC group.

The interaction of mannose-binding lectins (MBLs) with Candida albicans has been analyzed previously by microscopy and flow cytometry. We recently demonstrated that serum MBL levels vary during infection with Candida spp. and that serum MBLs are capable of interacting with yeast cell wall components. The aim of this study was to use, for the first time, surface plasmon resonance (SPR) technology to characterize the interaction between living label-free yeasts and non-mutated MBL purified from human serum. Our preliminary results demonstrate the robustness of this tool, which revealed specific and differential reactivities between the principal Candida spp. of medical interest. This model offers new perspectives as a tool for the characterization of yeast strains carrying mutations in gene coding for the mannosylation of fungal cell wall glycans and will enable better characterization of the interactions between C-lectins and glycan motifs expressed on the surface of yeasts.