Human Conventional and Plasmacytoid Dendritic Cells Differ in Their Ability to Respond to Saccharomyces cerevisiae.

Saccharomyces cerevisiae is a commensal yeast colonizer of mucosal surfaces and an emerging opportunistic pathogen in the mucosa and bloodstream. The role of S. cerevisiae has been largely characterized in peripheral blood mononuclear cells and monocyte-derived dendritic cells, where yeast cells induce the production of inflammatory cytokines through the interaction with mannose receptors, chitin receptors, DC SIGN, and dectin1. However, the response of blood-circulating dendritic cells (DCs) to S. cerevisiae has never been investigated. Among blood DCs, conventional DCs (cDCs) are producers of inflammatory cytokines, while plasmacytoid DCs (pDCs) are a specialized population producing a large amount of interferon (IFN)-α, which is involved in the antiviral immune response. Here we report that both human DC subsets are able to sense S. cerevisiae. In particular, cDCs produce interleukin (IL)-6, express activation markers, and promotes T helper 17 cell polarization in response to yeasts, behaving similarly to monocyte-derived DCs as previously described. Interestingly, pDCs, not cDCs, sense fungal nucleic acids, leading to the generation of P1-pDCs (PD-L1+CD80-), a pDC subset characterized by the production of IFN-α and the induction of a Th profile producing IL-10. These results highlight a novel role of pDCs in response to S. cerevisiae that could be important for the regulation of the host microbiota-immune system balance and of anti-fungal immune response.

Myeloid Derived Suppressor Cells Expansion Persists After Early ART and May Affect CD4 T Cell Recovery.

Myeloid-derived suppressor cells (MDSC) are expanded during HIV-1 infection and correlated with disease progression. MDSC expand in the early phase of primary infection depending on TRAIL level. In this study we evaluated the effect of ART on the frequency of MDSC in patients with primary HIV infection (PHI), and their impact on CD4 T cell reconstitution. MDSC frequency was evaluated by flow-cytometry in 60 PHI patients at 12, 24 and 48 weeks after ART initiation. Cytokine plasma levels were evaluated by Luminex technology at the same time points. The capacity of MDSC to modulate hematopoietic early progenitor cells' expansion was evaluated using the OP9/Dl1 in vitro system. As previously described, polymorphonuclear-MDSC (PMN-MDSC) frequency was higher in PHI compared to healthy donors. Interestingly, 48 weeks of successful ART failed to normalize the PMN-MDSC frequency. Moreover, PMN-MDSC frequency was not correlated with residual viral load, suggesting that the persistence of PMN-MDSC was not due to residual viral replication. Interestingly, patients with low PMN-MDSC frequency (<6%) at T0 had a higher HIV DNA at the same time point than individuals with high PMN-MDSC frequency (>6%). We also found an inverse correlation between PMN-MDSC frequency and CD4-T cell count at 48 weeks post-ART, which was confirmed by multivariate analysis adjusting for age and CD4 T cell number at baseline. These data suggest that the persistence of PMN-MDSC may impact CD4 T cell recovery. Indeed, in vitro PMN-MDSC impaired the expansion of CD34+CD38- hematopoietic early progenitors. Further, a balance between TRAIL and GM-CSF may be necessary to maintain a low MDSC level. In conclusion, early ART initiation was not able to normalize PMN-MDSC frequency that might impact the CD4 T cell recovery. These data open new questions regarding the clinical impact of MDSC persistence in HIV+ patients, in particular on non-AIDS related diseases.

Myeloid-Derived Suppressor Cells Specifically Suppress IFN-γ Production and Antitumor Cytotoxic Activity of Vδ2 T Cells.

γδ T cells represent less than 5% of circulating T cells; they exert a potent cytotoxic function against tumor or infected cells and secrete cytokines like conventional αß T cells. As αß T cells γδ T cells reside in the typical T cell compartments (the lymph nodes and spleen), but are more widely distributed in tissues throughout the body. For these reasons, some investigators are exploring the possibility of immunotherapies aimed to expand and activate Vδ2 T cells, or using them as Chimeric Antigen Receptor carriers. However, the role of immunosuppressive microenvironment on Vδ2 T cells during infections and cancers has not been completely elucidated. In particular, the effects of myeloid-derived suppressor cells (MDSC), largely expanded in such pathologies, were not explored. In the present work, we demonstrated that MDSC may inhibit IFN-γ production and degranulation of phosphoantigen-activated Vδ2 T cells. Moreover, the Vδ2 T cells cytotoxic activity against the Burkitt lymphoma cell line Daudi and Jurkat cell line were impaired by MDSC. The Arginase I seems to be involved in the impairment of Vδ2 T cell function induced by both tumor cells and MDSC. These data open a key issue in the context of Vδ2-targeted immunoteraphy, suggesting the need of combined strategies aimed to boost Vδ2 T cells circumventing tumor- and MDSC-induced Vδ2 T cells suppression.

Antennular Morphology and Contribution of Aesthetascs in the Detection of Food-related Compounds in the Shrimp Palaemon adspersus Rathke, 1837 (Decapoda: Palaemonidae).

Shrimp are an essential ecological component of marine ecosystems, and have commercial importance for human consumption and aquaculture. Like other decapod crustaceans, shrimp rely on chemical senses to detect and localize food resources by means of chemosensilla that are located mainly on the cephalothoracic appendages. Using the shrimp Palaemon adspersus, a model organism with omnivorous feeding behavior, we aimed to provide comparative information on the role of aesthetascs, antennular sensilla, and flicking behavior in food detection. To this end, we examined i) the morphology of antennular sensilla by field emission scanning electron microscopy, ii) the shrimp's sensitivity to a number of food-related compounds (amino acids and sugars) by means of whole-animal bioassays, and iii) the contribution of the aesthetasc sensilla to food detection. Our results showed that, aside from the aesthetascs, only three other main morphotypes of setae with chemoreceptive features were present in the antennules, thus accounting for relatively simple sensillar equipment. Nevertheless, we found broad-spectrum sensitivity of the shrimp to a number of amino acids (i.e., isoleucine, leucine, methionine, phenylalanine, glycine, tryptophan, cysteine, and tyrosine) and carbohydrates (trehalose, maltose, cellobiose, and fructose) that was consistent with the omnivorous or scavenging habits of the animal. Although aesthetasc ablation attenuated flicking behavior in a chemical stimulus-independent manner, success in detection and short-range localization of food did not rely on the presence of aesthetasc sensilla. This finding confirms the existence of a non-aesthetasc alternative pathway for feeding, with functional redundancy in simple generalist feeder models such as shrimp.

[Health Search--Research Institute of the Italian Society of General Practice: the creation of a research database in general practice]. / Health search--Istituto di ricerca della Società italiana di medicina generale: la realizzazione di un database per la ricerca in medicina generale.

OBJECTIVE: To describe a database used in general practice by analysing the characteristics of the physicians providing the data and the completeness of the data recording on the basis of the indicators of interest (smoking habits, weight, height, and the prevalence of hypertension). DESIGN: Descriptive study and multiple linear regression analysis of the relationships between structural variables and outcomes. SETTING: General practitioners (GPs) belonging to the Italian Society of General Medicine (SIMG), and enrolled in Health Search (HS). POPULATION: Six hundred and ninety-five voluntarily enrolled GPs and their patients. PRINCIPAL OUTCOMES: Descriptive statistics (mean and median values, standard deviation, frequencies) concerning the general characteristics of the GPs, the ways in which they connect to the network and their use of the clinical data management software, and epidemiological measures concerning the prevalence of hypertension among their patients, and the recording of weight, height and tobacco smoking habits. RESULTS: The geographic distribution of the GPs is homogeneous: 317 in Northern Italy (12.52 physicians per 10(6) patients), 134 in Central Italy (12.30 physicians per 10(6) patients) and 244 in Southern Italy and the Islands (11.89 physicians per 10(6) patients). Five hundred and ninety-five (85.6%) are males; their mean age is 46.7 years (SD +/- 3.8); the mean number of patients per physician is 1128; 69% have at least one post-graduate specialisation; 49% practise alone; and they work for a mean of 30 hours per week (SD +/- 13). Five hundred and fifty-three GPs were actually connected to the network as of January 2003. The data relating to the years 2000-2001 show an increase in the number of connected physicians (34 in 2000 and 261 in 2001) and in the number of connections (a median of 12 in 2000 and 17 in 2001). The GPs contact more than 80% of their patients every year. The frequency of the recording of data concerning smoking habits, weight and height increases in proportion with the frequency of connections. The prevalence of hypertension among the patients included in the survey is 5.4%. Multiple regression analysis showed that the variability in the prevalence of hypertension was not influenced by the frequency of PC use but by the different structure of the age classes of the patients. CONCLUSIONS: This study of the variables relating to GPs, their clinical practices, and their use of computerised records (examined by means of the chosen indicators) shows that the regular and complete recording of the principal data of health interest is feasible insofar as it is not biased by the characteristics of the GPs, and advantageous. The construction of the database therefore represents a first step towards the initiation of routine research into general practice in Italy.