Coagulase-negative staphylococci (CoNS) are a major cause of sepsis in the neonatal intensive care unit (NICU). We evaluated the hypothesis that the ica operon and biofilm production are associated with CoNS disease in this setting. CoNS associated with bacteremia or blood culture contamination and from the skin of infants with CoNS bacteremia or healthy controls were obtained during a prospective case-control study on a busy NICU. A total of 180 strains were identified, of which 122 (68%) were Staphylococcus epidermidis and the remainder were S. capitis (n ‫؍‬ 29), S. haemolyticus (n ‫؍‬ 11), S. hominis (n ‫؍‬ 9), S. warneri (n ‫؍‬ 8), and S. auricularis (n ‫؍‬ 1). The presence of the genes icaA, icaB, icaC, and icaD was determined by PCR, and biofilm production was examined using qualitative (Congo red agar [CRA]) and quantitative (microtiter plate) techniques. There were no significant differences in the presence of the ica operon or CRA positivity among the four groups of strains. However, quantitative biofilm production was significantly greater in strains isolated from either the blood or the skin of neonates with S. epidermidis bacteremia. We conclude that the quantity of biofilm produced may be associated with the ability to cause CoNS infection. This conclusion suggests that the regulation of biofilm expression may play a central role in the disease process.Coagulase-negative staphylococci (CoNS) are the major cause of late-onset sepsis in preterm infants (27,39,42,44). Approximately one in six very-low-birth-weight (Ͻ1,500-g) neonates develops an episode of CoNS bacteremia (21, 44), an event that is associated with a significant increase in morbidity and mortality (44), duration of hospital stay (18,21,44), and overall cost of treatment (44). There is thus a need to reduce the risk of sepsis in this setting, a goal which depends in part on defining the pathogenesis of infection.The role of biofilm formation as a determinant of CoNS infection has been the subject of ongoing study since the observation that some isolates of Staphylococcus epidermidis produced mucoid growth in vitro that adhered to the walls of culture tubes (2). A series of studies subsequently reported that this material, termed slime, was more commonly produced by isolates associated with sepsis, including intravenous-catheter-related bacteremia and other prosthetic device infections (5,6,10,14,28,31). The relevance to the neonatal intensive care unit (NICU) setting of slime production by CoNS isolates has been studied in relation to both carriage flora and isolates causing infection. The proportion of slime-producing CoNS in carriage flora increased on repeated sampling of neonates during the first 4 weeks of age in one unit (9) but did not vary in two other units over either 2 weeks (35) or a mean of 8 weeks (24). Endemic clones of CoNS that were associated with disease and that were slime producers were demonstrated to persist over a period of 10 years in one unit (26); however, carriage flora was not examined, and an association be...

Liver sinusoidal endothelial cells (LSEC) form a unique barrier between the liver sinusoids and the underlying parenchyma, and thus play a crucial role in maintaining metabolic and immune homeostasis, as well as actively contributing to disease pathophysiology. Whilst their endocytic and scavenging function is integral for nutrient exchange and clearance of waste products, their capillarisation and dysfunction precedes fibrogenesis. Furthermore, their ability to promote immune tolerance and recruit distinct immunosuppressive leukocyte subsets can allow persistence of chronic viral infections and facilitate tumour development. In this review, we present the immunological and barrier functions of LSEC, along with their role in orchestrating fibrotic processes which precede tumourigenesis. We also summarise the role of LSEC in modulating the tumour microenvironment, and promoting development of a pre-metastatic niche, which can drive formation of secondary liver tumours. Finally, we summarise closely inter-linked disease pathways which collectively perpetuate pathogenesis, highlighting LSEC as novel targets for therapeutic intervention.

Highlights d Hepatocytes engulf live CD4 + T cells, with a preference for regulatory cells d We called this process enclysis and compared it with known cell-in-cell processes d ICAM-1 and b-catenin accumulated at the point of T cell engulfment d Enclysis was seen in health, in liver cancer, and especially in autoimmune disorders

Coagulase-negative staphylococci (CoNS) are a leading cause of sepsis in the neonatal intensive care unit (NICU) setting. To evaluate the hypothesis that isolates of CoNS associated with disease belong to hypervirulent clones, as opposed to being drawn randomly from the neonatal unit carriage flora, we conducted a prospective, case-controlled study in a busy NICU. Using pulsed-field gel electrophoresis (PFGE), we compared the population structures of CoNS isolates associated with bacteremia with isolates from the skin of healthy and infected neonates and with blood culture contaminants. Endemic clones of CoNS were identified, but there was no difference in the distribution of the 6 species or 73 PFGE types between the carriage and disease isolate groups; this suggests that hypervirulent clones with an enhanced ability to cause disease were not present in this NICU setting.

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