Transcription factor C/EBPα is required for the development of Ly6Chi monocytes but not Ly6Clo monocytes

Monocytes comprise two major subsets, Ly6

Annual transcriptome of a key zooplankton species, the copepod Calanus finmarchicus

The copepod Calanus finmarchicus (Crustacea, Copepoda) is a key zooplanktonic species with a crucial position in the North Atlantic food web and significant contributor to ocean carbon flux. Like many other high latitude animals, it has evolved a programmed arrested development called diapause to cope with long periods of limited food supply, while growth and reproduction are timed to take advantage of seasonal peaks in primary production. However, anthropogenic warming is inducing changes in the expected timing of phytoplankton blooms, suggesting phenological mismatches with negative consequences for the N. Atlantic ecosystem. While diapause mechanisms are mainly studied in terrestrial arthropods, specifically on laboratory model species, such as the fruit fly Drosophila, the molecular investigations of annual rhythms in wild marine species remain fragmentary. Here we performed a rigorous year-long monthly sampling campaign of C. finmarchicus in a Scottish Loch (UK; 56.45°N, 5.18°W) to generate an annual transcriptome. The mRNA of 36 samples (monthly triplicate of 25 individuals) have been deeply sequenced with an average depth of 137 ± 4 million reads (mean ± SE) per sample, aligned to the reference transcriptome, and filtered. We detail the quality assessment of the datasets and provide a high-quality resource for the investigation of wild annual transcriptomic rhythms (35,357 components) in a key diapausing zooplanktonic species

IL-6 selectively suppresses cDC1 specification via C/EBPβ

Cytokines produced in association with tumors can impair antitumor immune responses by reducing the abundance of type 1 conventional dendritic cells (cDC1), but the mechanism remains unclear. Here, we show that tumor-derived IL-6 generally reduces cDC development but selectively impairs cDC1 development in both murine and human systems through the induction of C/EBPβ in the common dendritic cell progenitor (CDP). C/EBPβ and NFIL3 compete for binding to sites in the Zeb2 -165 kb enhancer and support or repress Zeb2 expression, respectively. At homeostasis, pre-cDC1 specification occurs upon Nfil3 induction and consequent Zeb2 suppression. However, IL-6 strongly induces C/EBPβ expression in CDPs. Importantly, the ability of IL-6 to impair cDC development is dependent on the presence of C/EBPβ binding sites in the Zeb2 -165 kb enhancer, as this effect is lost in Δ1+2+3 mutant mice in which these binding sites are mutated. These results explain how tumor-associated IL-6 suppresses cDC1 development and suggest therapeutic approaches preventing abnormal C/EBPβ induction in CDPs may help reestablish cDC1 development to enhance antitumor immunity

Shared pathway of WDFY4-dependent cross-presentation of immune complexes by cDC1 and cDC2

Priming CD8+ T cells against tumors or viral pathogens results largely from cross-presentation of exogenous antigens by type 1 conventional dendritic cells (cDC1s). Although monocyte-derived DCs and cDC2s can cross-present in vitro, their physiological relevance remains unclear. Here, we used genetic models to evaluate the role of cDC subsets in presentation of cell-associated and immune complex antigens to CD4+ and CD8+ T cells in vivo. For cell-associated antigens, cDC1s were necessary and sufficient to prime both CD4+ and CD8+ T cells. In contrast, for immune complex antigens, either cDC1 or cDC2, but not monocyte-derived DCs, could carry out cross-presentation to CD8+ T cells. Mice lacking cDC1 and vaccinated with immune complexes could cross-prime CD8+ T cells that were sufficient to mediate tumor rejection. Notably, this cross-presentation mediated by cDC2 was also WDFY4 dependent, similar to cross-presentation of cell-associated antigens by cDC1. These results demonstrate a previously unrecognized activity of WDFY4 in cDC2s and suggest a cross-presentation pathway shared by cDC subsets

Hepatitis A outbreak disproportionately affecting men who have sex with men (MSM) in the European Union and European Economic Area, June 2016 to May 2017

Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205254/Between 1 June 2016 and 31 May 2017, 17 European Union (EU) and European Economic Area countries reported 4,096 cases associated with a multi-country hepatitis A (HA) outbreak. Molecular analysis identified three co-circulating hepatitis A virus (HAV) strains of genotype IA: VRD_521_2016, V16-25801 and RIVM-HAV16-090. We categorised cases as confirmed, probable or possible, according to the EU outbreak case definitions. Confirmed cases were infected with one of the three outbreak strains. We investigated case characteristics and strain-specific risk factors for transmission. A total of 1,400 (34%) cases were confirmed; VRD_521_2016 and RIVM-HAV16-090 accounted for 92% of these. Among confirmed cases with available epidemiological data, 92% (361/393) were unvaccinated, 43% (83/195) travelled to Spain during the incubation period and 84% (565/676) identified as men who have sex with men (MSM). Results depict an HA outbreak of multiple HAV strains, within a cross-European population, that was particularly driven by transmission between non-immune MSM engaging in high-risk sexual behaviour. The most effective preventive measure to curb this outbreak is HAV vaccination of MSM, supplemented by primary prevention campaigns that target the MSM population and promote protective sexual behaviour.info:eu-repo/semantics/publishedVersio