The effector T cell response to influenza infection

Influenza virus infection induces a potent initial innate immune response, which serves to limit the extent of viral replication and virus spread. However, efficient (and eventual) viral clearance within the respiratory tract requires the subsequent activation, rapid proliferation, recruitment, and expression of effector activities by the adaptive immune system, consisting of antibody producing B cells and influenza-specific T lymphocytes with diverse functions. The ensuing effector activities of these T lymphocytes ultimately determine (along with antibodies) the capacity of the host to eliminate the viruses and the extent of tissue damage. In this review, we describe this effector T cell response to influenza virus infection. Based on information largely obtained in experimental settings (i.e., murine models), we will illustrate the factors regulating the induction of adaptive immune T cell responses to influenza, the effector activities displayed by these activated T cells, the mechanisms underlying the expression of these effector mechanisms, and the control of the activation/differentiation of these T cells, in situ, in the infected lungs

Decreased renal accumulation of aminoglycoside reflects defective receptor-mediated endocytosis in cystic fibrosis and Dent's disease

The clinical use of aminoglycoside (AG) antibiotics is limited by their renal toxicity, which is caused by drug accumulation in proximal tubule (PT) cells. Clinical studies reported that renal clearance of AG is enhanced in cystic fibrosis (CF) patients, which might reflect the role of CFTR in PT cell endocytosis. In order to assess the role of chloride transporters on the renal handling of AG, we investigated gentamicin uptake and renal accumulation in mice lacking functional CFTR (Cftr ( ∆F/∆F)) or knock-out for the Cl(-)/H(+) exchanger ClC-5 (Clcn5 ( Y/- )). The latter represent a paradigm of PT dysfunction and defective receptor-mediated endocytosis. As compared with controls, Cftr ( ∆F/∆F) and Clcn5 ( Y/- ) mice showed a 15% to 85% decrease in gentamicin accumulation in the kidney, respectively, in absence of renal failure. Studies on primary cultures of Cftr ( ∆F/∆F) and Clcn5 ( Y/- ) mouse PT cells confirmed the reduction in gentamicin uptake, although colocalization with endosomes and lysosomes was maintained. Quantification of endocytosis in PT cells revealed that gentamicin, similar to albumin, preferentially binds to megalin. The functional loss of ClC-5 or CFTR was reflected by a decrease of the endocytic uptake of gentamicin, with a more pronounced effect in cells lacking ClC-5. These results support the concept that CFTR, as well as ClC-5, plays a relevant role in PT cell endocytosis. They also demonstrate that the functional loss of these two chloride transporters is associated with impaired uptake of AG in PT cells, reflected by a decreased renal accumulation of the drug

E-government implementation: A bird’s eye view of issues relating to costs, opportunities, benefits and risks

NoAfter more than a decade of comprehensive research work in the area of electronic government (e-government), no attempt has yet been made to undertake a systematic literature review on the costs, opportunities, benefits and risks that influence the implementation of e-government. This is particularly significant given the various related challenges that governments have faced over the years when implementing e-government initiatives. Hence, the aim of this paper is to undertake a comprehensive analysis of relevant literature addressing these issues using a systematic review of 132 studies identified from the Scopus online database and Google Scholar together with a manual review of relevant papers from journals dedicated to electronic government research such as Electronic Government, an International Journal (EGIJ), International Journal of Electronic Government Research (IJEGR) and Transforming Government: People, Process, and Policy (TGPPP). The overall review indicated that although a large number of papers discuss costs, opportunities, benefits and risks, treatment of these issues have tended to be superficial. Moreover, there is a lack of empirical studies which can statistically evaluate the performance of these constructs in relation to the various e-government systems. Therefore, this research would help governments to better analyse the impact of costs, opportunities, benefits and risks on the success of e-government systems and its pre-adoption from an implementation perspective