Multiple comparisons were conducted using the Tukey test on the fitted data

bly the expression of other negative regulators such as USP18. This adds another layer of complexity to IFN regulation, and clearly requires further study. The consequences of HCV mediated AXL up-regulation are not limited to regulation of IFN signalling. Up-regulation of AXL is well documented in hepatocellular carcinoma, and contributes to HCC cell line proliferation, migration and invasion, through activation of AKT and MAPK signalling pathways. Moreover, AXL serves as an entry factor for a number of enveloped viruses, including the related dengue flavivirus. If the same is true for HCV, immune-driven AXL expression in hepatocytes in the HCV infected liver could facilitate the spread of the virus into uninfected cells. In summary, we have shown that AXL is induced by HCV infection, and is capable of regulating the ISG response to HCV in hepatocytes. The immunomodulatory role of AXL in the context of IFNL3/4 polymorphisms remains uncertain, but may provide a mechanism for the differences observed in hepatic and blood ISG regulation, based on the dominant IFNs in each cell type. Tuberculosis, caused by infection with 1268798 site Mycobacterium tuberculosis remains one of the world’s deadliest diseases, killing an estimated 1.5 million people annually. Whereas drugsusceptible forms of the disease are in principle curable, the duration of treatment courses is at least 6 months and may last years. Multidrug resistant TB and extensively drug resistant TB have poorer and less certain outcomes. It is expected that shortened antituberculosis treatment regimens will improve patient adherence to treatment, and thereby foster better case management and disease control and minimize the risk of drug resistance. An interesting aspect of long-term chemotherapy in TB is that, whereas more than 95% of the tubercle bacilli population detectable in a patient’s sputum can be cleared in the first few days of treatment, prolonged treatment is required to eradicate the residual minority 1 / 16 Confinement-Induced Drug-Tolerance in Mycobacteria population using drugs that are rapidly potent in vitro. Overcoming this bacterial persistence is central to shortening TB treatment. PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19729663 The transient nature of persistence–an epigenetic drug-tolerance phenotype–has pushed research in this area toward miniaturization and chip-based control using time-lapse microscopy to study the phenotypic heterogeneity within bacterial populations in situ. Whereas these efforts have thus far investigated persistence in an extracellular context, recent studies have shown that the intracellular mycobacterial sub-population, which makes up an essential component of human TB infection, is significantly more tolerant to antibiotics. Separate studies have shown that the dimensions and diffusional characteristics of the growth environment can influence bacterial gene expression. To investigate persistence, we characterized the growth and drug susceptibility of mycobacteria replicating in space-confined microfabricated cell culture environments to mimic the confinement experienced by mycobacteria replicating within macrophages. We focused our experiments on Mycobacterium smegmatis, an experimentally tractable surrogate for M. tuberculosis with respect to rifampicin–a frontline drug in TB treatment. The PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19728363 microdialyser has a micro-sized cell culture chamber that is 200 picoliters in volume to approximate the ~5pL volume of the membrane-bound compartment of human macrophages. Thus upon inoculation of a mic