Interaction of Pattern Recognition Receptors with Mycobacterium Tuberculosis.

Tuberculosis (TB) is considered a major worldwide health problem with 10 million new cases diagnosed each year. Our understanding of TB immunology has become greater and more refined since the identification of Mycobacterium tuberculosis (MTB) as an etiologic agent and the recognition of new signaling pathways modulating infection. Understanding the mechanisms through which the cells of the immune system recognize MTB can be an important step in designing novel therapeutic approaches, as well as improving the limited success of current vaccination strategies. A great challenge in chronic disease is to understand the complexities, mechanisms, and consequences of host interactions with pathogens. Innate immune responses along with the involvement of distinct inflammatory mediators and cells play an important role in the host defense against the MTB. Several classes of pattern recognition receptors (PRRs) are involved in the recognition of MTB including Toll-Like Receptors (TLRs), C-type lectin receptors (CLRs) and Nod-like receptors (NLRs) linked to inflammasome activation. Among the TLR family, TLR1, TLR2, TLR4, and TLR9 and their down-stream signaling proteins play critical roles in the initiation of the immune response in the pathogenesis of TB. The inflammasome pathway is associated with the coordinated release of cytokines such as IL-1β and IL-18 which also play a role in the pathogenesis of TB. Understanding the cross-talk between these signaling pathways will impact on the design of novel therapeutic strategies and in the development of vaccines and immunotherapy regimes. Abnormalities in PRR signaling pathways regulated by TB will affect disease pathogenesis and need to be elucidated. In this review we provide an update on PRR signaling during M. tuberculosis infection and indicate how greater knowledge of these pathways may lead to new therapeutic opportunities

A variety of cytokines and immunologically relevant surface molecules are expressed by normal human skeletal muscle cells under proinflammatory stimuli

Muscle is an attractive target for gene therapy and for immunization with DNA vaccines and is also the target of immunological injury in myositis. It is important therefore to understand the immunologic capabilities of muscle cells themselves. In this study, we show that proinflammatory stimuli induce the expression of other cytokines such as IL-6, transforming growth factor-beta (TGF-β), and granulocyte-macrophage colony-stimulating factor (GM-CSF) by muscle cells themselves, as well as the up-regulation of human leucocyte antigen (HLA) class I, class II and intercellular adhesion molecule-1 (ICAM-1). Thus, muscle cells have an inherent ability to express and respond to a variety of cytokines and chemokines. The levels of HLA class I, class II and ICAM-1 in inflamed muscle may be affected by the secreted products of the stimulation

Editorial: on the road to multi-modal and pluri-disciplinary treatment of glioblastomas.

Despite major advances in the management of malignant gliomas of which glioblastomas represent the ultimate grade of malignancy, they remain incurable. Indeed, glioblastoma patients have a median survival expectancy of only 14 months on the current standard treatment of surgical resection to the extent which is feasible, followed by adjuvant radiotherapy plus temozolomide given concomitantly with and after radiotherapy (Lefranc et al. J Clin Oncol 23:2411-2422, 2005; Expert Rev Anticancer Ther 6:719-732, 2006; Stummer et al. Neurosurgery 62:564-576, 2008). Accordingly, the present editorial discusses (1) the high cell motility and resistance to apoptosis which characterise glioblastoma growth and malignancy with respect to the failure of conventional therapy, (2) ways to overcome apoptosis resistance and the real hope offered by temozolomide, (3) targeted chemotherapeutic approaches and the disappointing results obtained in monotherapy but their potential in combination therapy, (4) anti-migratory strategies that could supplement conventional therapy notably by inhibiting a new target; the alpha1 subunit of the sodium pump, (5) dendritic cell therapy, (6) cancer stem cell targeting and finally (7) topical therapies and new surgical approaches for more radical resection which could be used to complement multi-modal treatments within a multi-disciplinary approach.Editorialinfo:eu-repo/semantics/publishe

Microbubble moving in blood flow in microchannels: effect on the cell-free layer and cell local concentration

Gas embolisms can hinder blood flow and lead to occlusion of the vessels and ischemia. Bubbles in microvessels circulate as tubular bubbles (Taylor bubbles) and can be trapped, blocking the normal flow of blood. To understand how Taylor bubbles flow in microcirculation, in particular, how bubbles disturb the blood flow at the scale of blood cells, experiments were performed in microchannels at a low Capillary number. Bubbles moving with a stream of in vitro blood were filmed with the help of a high-speed camera. Cell-free layers (CFLs) were observed downstream of the bubble, near the microchannel walls and along the centerline, and their thicknesses were quantified. Upstream to the bubble, the cell concentration is higher and CFLs are less clear. While just upstream of the bubble the maximum RBC concentration happens at positions closest to the wall, downstream the maximum is in an intermediate region between the centerline and the wall. Bubbles within microchannels promote complex spatio-temporal variations of the CFL thickness along the microchannel with significant relevance for local rheology and transport processes. The phenomenon is explained by the flow pattern characteristic of low Capillary number flows. Spatio-temporal variations of blood rheology may have an important role in bubble trapping and dislodging.The authors acknowledge the financial support provided by PTDC/SAU-BEB/105650/2008, PTDC/SAU-ENB/ 116929/2010, EXPL/EMS-SIS/2215/2013 and PTDC/QEQ-FTT/4287/ 2014 from FCT (Science and Technology Foundation), COMPETE, QREN and European Union (FEDER).info:eu-repo/semantics/publishedVersio