Decreased Type I Interferon Production by Plasmacytoid Dendritic Cells Contributes to Severe Dengue

The clinical presentation of dengue virus (DENV) infection is variable. Severe complications mainly result from exacerbated immune responses. Type I interferons (IFN-I) are important in antiviral responses and form a crucial link between innate and adaptive immunity. Their contribution to host defense during DENV infection remains under-studied, as direct quantification of IFN-I is challenging. We combined ultra-sensitive single-molecule array (Simoa) digital ELISA with IFN-I gene expression to elucidate the role of IFN-I in a well-characterized cohort of hospitalized Cambodian children undergoing acute DENV infection. Higher concentrations of type I IFN proteins were observed in blood of DENV patients, compared to healthy donors, and correlated with viral load. Stratifying patients for disease severity, we found a decreased expression of IFN-I in patients with a more severe clinical outcome, such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). This was seen in parallel to a correlation between low IFNα protein concentrations and decreased platelet counts. Type I IFNs concentrations were correlated to frequencies of plasmacytoid DCs, not DENV-infected myloid DCs and correlated inversely with neutralizing anti-DENV antibody titers. Hence, type I IFN produced in the acute phase of infection is associated with less severe outcome of dengue disease

Test of protected silver coating on aluminum samples of ARIEL main telescope mirror substrate material

Ariel (Atmospheric Remote-Sensing Infrared Exoplanet Large Survey) has been adopted as the M4 mission for ESA \u201cCosmic Vision\u201d program. Launch is scheduled for 2029. ARIEL will study exoplanet atmospheres through transit spectroscopy with a 1 m class telescope optimized in the waveband between 1.95 and 7.8 \u3bcm and operating in cryogenic conditions in the temperature range 40-50 K. Aluminum alloy 6061, in the T651 temper, was chosen as baseline material for telescope mirror substrates and supporting structures, following a trade-off study. To improve mirrors reflectivity within the operating waveband and to protect the aluminum surface from oxidation, a protected silver coating with space heritage was selected and underwent a qualification campaign during Phase B1 of the mission, with the goal of demonstrating a sufficient level of technology maturity. The qualification campaign consisted of two phases: a first set of durability and environmental tests conducted on a first batch of coated aluminum samples, followed by a set of verification tests performed on a second batch of samples coated alongside a full-size demonstrator of Ariel telescope primary mirror. This study presents the results of the verification tests, consisting of environmental (humidity and temperature cycling) tests and chemical/mechanical (abrasion, adhesion, cleaning) tests performed on the samples, and abrasion tests performed on the demonstrator, by means of visual inspections and reflectivity measurements

PSMB10, the last immunoproteasome gene missing for PRAAS

We describe a patient exhibiting clinical features of PRAAS due to a homozygous mutation in PSMB10. This gene encodes the only immunoproteasome subunit in which mutations have not yet been associated with PRAAS

HIV DNA reservoir and elevated PD-1 expression of CD4 T-cell subsets particularly persist in the terminal ileum of HIV-positive patients despite cART

Objectives Despite its importance as an HIV anatomic sanctuary, little is known about the characteristics of the HIV reservoir in the terminal ileum (TI). In blood, the immune checkpoint inhibitor programmed-death-1 (PD-1) has been linked to the HIV reservoir and T-cell immune dysfunction. We thus evaluated PD-1 expression and cell-associated HIV DNA in memory CD4 T-cell subsets from TI, peripheral blood (PB) and rectum (RE) of untreated and treated HIV-positive patients to identify associations between PD-1 and HIV reservoir in other sites. Methods Using mononuclear cells from PB, TI and RE of untreated HIV-positive (N = 6), treated (n = 18) HIV-positive and uninfected individuals (n = 16), we identified and sorted distinct memory CD4 T-cell subsets by flow cytometry, quantified their cell-associated HIV DNA using quantitative PCR and assessed PD-1 expression levels using geometric mean fluorescence intensity. Combined HIV-1 RNA in situ hybridization and immunohistochemistry was performed on ileal biopsy sections. Results Combined antiretroviral therapy (cART)-treated patients with undetectable HIV RNA and significantly lower levels of HIV DNA in PB showed particularly high PD-1 expression in PB and TI, and high HIV DNA levels in TI, irrespective of clinical characteristics. By contrast, in treatment-naive patients HIV DNA levels in memory CD4 T-cell subsets were high in PB and TI. Conclusion Elevated PD-1 expression on memory CD4 T-cells in PB and TI despite treatment points to continuous immune dysfunction and underlines the importance of evaluating immunotherapy in reversing HIV latency and T-cell reconstitution. As HIV DNA particularly persists in TI despite cART, investigating samples from TI is crucial in understanding HIV immunopathogenesis