Macrophage polarisation affects their regulation of trophoblast behaviour

Introduction During the first trimester of human pregnancy, fetally-derived extravillous trophoblast (EVT) cells invade into uterine decidua and remodel the uterine spiral arteries to ensure that sufficient blood reaches the maternal-fetal interface. Decidual macrophages have been implicated in the regulation of decidual remodelling and aberrant activation of these immune cells is associated with pre-eclampsia. Methods The monocytic cell line THP-1 was activated to induce an M1 or M2 phenotype and the conditioned media was used to treat the EVT cell line SGHPL-4 in order to determine the effect of macrophage polarisation on trophoblast behaviour in-vitro. SGHPL-4 cell functions were assessed using time-lapse microscopy, endothelial-like tube formation assays and western blot. Results The polarisation state of the THP-1 cells was found to differentially alter the behaviour of trophoblast cells in-vitro with pro-inflammatory M1 conditioned media significantly inhibiting trophoblast motility, impeding trophoblast tube formation, and inducing trophoblast expression of caspase 3, when compared to anti-inflammatory M2 conditioned media. Discussion Macrophages can regulate trophoblast functions that are critical during decidual remodelling in early pregnancy. Importantly, there is differential regulation of trophoblast function in response to the polarisation state of these cells. Our studies indicate that the balance between a pro- and anti-inflammatory environment is important in regulating the cellular interactions at the maternal-fetal interface and that disturbances in this balance likely contribute to pregnancy disorders associated with poor trophoblast invasion and vessel remodelling

Decoration of the enterococcal polysaccharide antigen EPA is essential for virulence, cell surface charge and interaction with effectors of the innate immune system

Enterococcus faecalis is an opportunistic pathogen with an intrinsically high resistance to lysozyme, a key effector of the innate immune system. This high level of resistance requires a complex network of transcriptional regulators and several genes (oatA, pgdA, dltA and sigV) acting synergistically to inhibit both the enzymatic and cationic antimicrobial peptide activities of lysozyme. We sought to identify novel genes modulating E. faecalis resistance to lysozyme. Random transposon mutagenesis carried out in the quadruple oatA/pgdA/dltA/sigV mutant led to the identification of several independent insertions clustered on the chromosome. These mutations were located in a locus referred to as the enterococcal polysaccharide antigen (EPA) variable region located downstream of the highly conserved epaA-epaR genes proposed to encode a core synthetic machinery. The epa variable region was previously proposed to be responsible for EPA decorations, but the role of this locus remains largely unknown. Here, we show that EPA decoration contributes to resistance towards charged antimicrobials and underpins virulence in the zebrafish model of infection by conferring resistance to phagocytosis. Collectively, our results indicate that the production of the EPA rhamnopolysaccharide backbone is not sufficient to promote E. faecalis infections and reveal an essential role of the modification of this surface polymer for enterococcal pathogenesis

Deviating flora of tinea capitis in Western China suggests slow migration rates in dermatophytes.

Tinea capitis is a common dermatophyte infection of the scalp of children in Western China, with the gray-patch from being the most prevalent. Twenty years ago, the most widespread etiologic agent was reported to be Trichophyton violaceum, which was later succeeded by Microsporum ferrugineum and Trichophyton schoenleinii. In the framework of our recent study, 97 isolates were collected from patients with clinically suspected tinea capitis. Identification was performed by conventional methods and by sequencing the ribosomal DNA internal transcribed spacer region. In the case of T. violaceum an additional microsatellite primer set (T1) was used. Five species (in order of frequency, Trichophyton violaceum, T. schoenleinii, Microsporum ferrugineum, zoophilic strains of Arthroderma vanbreuseghemii, and Trichophyton tonsurans) were identified. Results of molecular and phenotypic ID of the same strains showed good correspondence. Comparison with earlier data showed that dermatophytes species in former rural societies must have migrated extremely slowly. Preponderance of local transmission from domesticated animals was proven by the occurrence of zoophilic strains of Arthroderma vanbreuseghemii. Etiologic agents in the rural communities of Western China tend to be different from those of the other regions in the country, despite modern communication and traffic