Bacterial lipopolysaccharide inhibits influenza virus infection of human macrophages and the consequent induction of CD8+ T cell immunity

Item does not contain fulltextIt is well established that infection with influenza A virus (IAV) facilitates secondary bacterial disease. However, there is a growing body of evidence that the microbial context in which IAV infection occurs can affect both innate and adaptive responses to the virus. To date, these studies have been restricted to murine models of disease and the relevance of these findings in primary human cells remains to be elucidated. Here, we show that pre-stimulation of primary human monocyte-derived macrophages (MDMs) with the bacterial ligand lipopolysaccharide (LPS) reduces the ability of IAV to infect these cells. The inhibition of IAV infection was associated with a reduced transcription of viral RNA and the ability of LPS to induce an anti-viral/type I interferon response in human MDMs. We demonstrated that this reduced rate of viral infection is associated with a reduced ability to present a model antigen to autologous CD8+ T cells. Taken together, these data provide the first evidence that exposure to bacterial ligands like LPS can play an important role in modulating the immune response of primary human immune cells towards IAV infection, which may then have important consequences for the development of the host's adaptive immune response

Quantitative considerations in medium energy ion scattering depth profiling analysis of nanolayers

The high depth resolution capability of medium energy ion scattering (MEIS) is becoming increasingly relevant to the characterisation of nanolayers in e.g. microelectronics. In this paper we examine the attainable quantitative accuracy of MEIS depth profiling. Transparent but reliable analytical calculations are used to illustrate what can ultimately be achieved for dilute impurities in a silicon matrix and the significant element-dependence of the depth scale, for instance, is illustrated this way. Furthermore, the signal intensity-to-concentration conversion and its dependence on the depth of scattering is addressed. Notably, deviations from the Rutherford scattering cross section due to screening effects resulting in a non-coulombic interaction potential and the reduction of the yield owing to neutralization of the exiting, backscattered H+ and He+ projectiles are evaluated. The former mainly affects the scattering off heavy target atoms while the latter is most severe for scattering off light target atoms and can be less accurately predicted. However, a pragmatic approach employing an extensive data set of measured ion fractions for both H+ and He+ ions scattered off a range of surfaces, allows its parameterization. This has enabled the combination of both effects, which provides essential information regarding the yield dependence both on the projectile energy and the mass of the scattering atom. Although, absolute quantification, especially when using He+, may not always be achievable, relative quantification in which the sum of all species in a layer add up to 100%, is generally possible. This conclusion is supported by the provision of some examples of MEIS derived depth profiles of nanolayers. Finally, the relative benefits of either using H+ or He+ ions are briefly considered

A Novel Method Linking Antigen Presentation by Human Monocyte-Derived Macrophages to CD8(+) T Cell Polyfunctionality.

Contains fulltext : 128627.pdf (publisher's version ) (Open Access)To understand the interactions between innate and adaptive immunity, and specifically how virally infected macrophages impact T cell function, novel assays examining the ability of macrophages to present antigen to CD8(+) T cells are needed. In the present study, we have developed a robust in vitro assay to measure how antigen presentation by human monocyte-derived macrophages (MDMs) affects the functional capacity of autologous CD8(+) T cells. The assay is based on the polyfunctional characteristics of antigen-specific CD8(+) T cells, and is thus called a Mac-CD8 Polyfunctionality Assay. Following purification of monocytes and their maturation to MDMs, MDMs were pulsed with an antigenic peptide to be presented to CD8(+) T cells. Peptide-pulsed MDMs were then incubated with antigen-specific CD8(+) T cells in order to assess the efficacy of antigen presentation to T cells. CD8(+) T cell polyfunctionality was assessed by staining with mAbs to IFN-gamma, TNF-alpha, and CD107a in a multi-color intracellular cytokine staining assay. To highlight the utility of the Mac-CD8 Polyfunctionality Assay, we assessed the effects of influenza infection on the ability of human macrophages to present antigen to CD8(+) T cells. We found that influenza infection of human MDMs can alter the effector efficacy of MDMs to activate more CD8(+) T cells with cytotoxic capacity. This has important implications for understanding how the virus-infected macrophages affect adaptive immunity at the site of infection

Spatial unemployment and differences in excess demand A further analysis

SIGLELD:3597.993(3) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Artificial rearing of goat kids Effects of weaning age and other factors

2 volsSIGLEAvailable from British Library Lending Division - LD:D53999/85 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Problems of regional transformation and deindustrialisation in the European Community

SIGLEAvailable from British Library Document Supply Centre- DSC:3597.993(45) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Causal factors in European urban changes 1971 to 1988

SIGLEAvailable from British Library Document Supply Centre- DSC:3597.993(44) / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Endocytic function is critical for influenza A virus infection via DC-SIGN and L-SIGN

10.1038/srep19428Scientific Reports61942