Rab14 regulates the maturation of macrophage phagosomes containing the fungal pathogen Candida albicans and the outcome of the host-pathogen interaction

Date of Acceptance: 02/02/2015 Copyright © 2015, American Society for Microbiology. All Rights Reserved.Peer reviewedPublisher PD

SOCS3 is a modulator of human macrophage phagocytosis

ACKNOWLEDGMENTS This work was supported by Kidney Research UK (Grant Number RP1/2012). The authors thank the staff of the Aberdeen Microscopy and Histology Core Facility for advice and technical assistance. The authors acknowledge and are grateful to all volunteers for donating blood for macrophage and neutrophil isolation.Peer reviewedPublisher PD

Kinetic studies of Candida parapsilosis phagocytosis by macrophages and detection of intracellular survival mechanisms

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Ybp1 and Gpx3 signaling in Candida albicans govern hydrogen peroxide-induced oxidation of the Cap1 transcription factor and macrophage escape

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Pho4 mediates phosphate acquisition in Candida albicans and is vital for stress resistance and metal homeostasis

ACKNOWLEDGMENTS We thank Karl Kuchler for the C. albicans superoxide dismutase mutants used in this study. This work was funded by a Medical Research Council Doctoral Training Program studentship to M.A.C.I.; Wellcome Trust Grants 089930 to J.Q., 080088 to A.J.P.B., and 097377 to J.Q., A.J.P.B., and L.P.E.; Biotechnology and Biological Sciences Research Council Grants BB/K016393/1 to J.Q. and BB/F00513X/1 and BB/K017365/1 to A.J.P.B.; European Research Council STRIFE Advanced Grant ERC-2009-AdG-249793 to A.J.P.B.; and Wellcome Trust and Royal Society Sir Henry Dale Fellowship 098375/Z/12/Z to K.J.W. and E.T. The funders had no role in study design, data collection, or interpretation or the decision to submit the work for publication.Peer reviewedPublisher PD

Novel insights into host-fungal pathogen interactions derived from live-cell imaging

Acknowledgments The authors acknowledge funding from the Wellcome Trust (080088, 086827, 075470 and 099215) including a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377 and FP7-2007–2013 grant agreement HEALTH-F2-2010-260338–ALLFUN to NARG.Peer reviewedPublisher PD

Macrophage programming in inflammatory disease

Before embarking on the work presented here I showed that certain activating signals, such as IFN-g and TNF-a programmed macrophages to develop distinct sets of properties in vitro, which included unresponsiveness to other types of activation.  This raised the question whether macrophage programming occurs in passive and active renal inflammation and whether the macrophage programme could be biased by systemic administration of cytokines. The data presented here shows that macrophages infiltrating acutely inflamed glomeruli of rats with nephrotoxic nephritis display programmed behaviour:  operationally they behave as though programmed by IFN-g, and maintain these characteristics despite systematic administration of anti-inflammatory cytokines such as IL-4 or TGF-b.  This triggered further studies using a model of mesangioproliferative nephritis that can be adapted to induce resolving or progressive glomerular injury.  These show that glomerular localisation does not always induce macrophage programming and that whether macrophages become programmed or not depends on the nature of the injury.  Furthermore the data shows that macrophages become committed to a particular programme shortly after entering a programming environment. These observations raise question about the factors that induce macrophage programming at early stages of inflammatory disease and its consequences for its outcome.  It provides an important mechanistic insight into how macrophage functional development is influenced by the underlying disease process.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Pathophysiological importance of antineutrophil antibodies in vasculitis

Purpose of review: We endeavour to provide a brief overview of the recent advances in understanding of how antineutrophil cytoplasmic antibodies (ANCAs) contribute to the pathophysiology of vasculitis. Recent findings: Substantial progress has been made in our understanding of the immunopathogenesis of ANCA-associated vasculitides. Compelling evidence from in-vitro studies and experimental models in conjunction with clinical trials has confirmed that ANCAs directly contribute to the evolution and progression of the disease process. A new ANCA, directed against human lysosome membrane protein-2 (LAMP-2), has recently been described as a sensitive and specific marker for renal vasculitis and we discuss its potential impact for diagnosis and therapy. Furthermore, high-throughput approaches are starting to identify genetic patterns that may identify patients likely to respond to specific therapy or having a high probability of relapse. Summary: It has become increasingly clear over the last two decades that ANCA IgG is pathogenic in vasculitis. Novel therapies aimed at selected cell populations or blocking specific pathogenic pathways offer hope for more selectively treating this heterogeneous group of patients, while avoiding nonspecific immunosuppression and its adverse effects