58 results found
Bercusson A, Colley T, Shah A, et al., 2018, Ibrutinib blocks Btk-dependent NF-ĸB and NFAT responses in human macrophages during Aspergillus fumigatus phagocytosis., Blood, Vol: 132, Pages: 1985-1988
Abdolrasouli A, Scourfield A, Rhodes J, et al., 2018, High prevalence of triazole resistance in clinical Aspergillus fumigatus isolates in a specialist cardiothoracic centre, INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, Vol: 52, Pages: 637-642, ISSN: 0924-8579
Santiago V, Rezvani K, Sekine T, et al., 2018, Human NK Cells Develop an Exhaustion Phenotype During Polar Degranulation at the Aspergillus fumigatus Hyphal Synapse, FRONTIERS IN IMMUNOLOGY, Vol: 9, ISSN: 1664-3224
Nwankwo L, Periselneris J, Cheong J, et al., 2018, A Prospective Real-World Study of the Impact of an Antifungal Stewardship Program in a Tertiary Respiratory-Medicine Setting, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol: 62, ISSN: 0066-4804
Abdolrasouli A, Petrou MA, Park H, et al., 2018, Surveillance for Azole-Resistant Aspergillus fumigatus in a Centralized Diagnostic Mycology Service, London, United Kingdom, 1998-2017, FRONTIERS IN MICROBIOLOGY, Vol: 9, ISSN: 1664-302X
Abdolrasouli A, Bercusson AC, Rhodes JL, et al., 2018, Airway persistence by the emerging multi-azole-resistant Rasamsonia argillacea complex in cystic fibrosis, MYCOSES, Vol: 61, Pages: 665-673, ISSN: 0933-7407
Rhodes J, Abdolrasouli A, Farrer RA, et al., 2018, Genomic epidemiology of the UK outbreak of the emerging human fungal pathogen Candida auris (vol 7, pg 43, 2018), EMERGING MICROBES & INFECTIONS, Vol: 7, ISSN: 2222-1751
Colley T, Sehra G, Chowdhary A, et al., 2018, In Vitro and In Vivo Efficacy of a Novel and Long-Acting Fungicidal Azole, PC1244, on Aspergillus fumigatus Infection, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol: 62, ISSN: 0066-4804
Eades CP, Armstrong-James DPH, Periselneris J, et al., 2018, Improvement in Exophiala dermatitidis airway persistence and respiratory decline in response to interferon-gamma therapy in a patient with cystic fibrosis., J Cyst Fibros, Vol: 17, Pages: e32-e34
Rhodes J, Abdolrasouli A, Farrer RA, et al., 2018, Genomic epidemiology of the UK outbreak of the emerging human fungal pathogen Candida auris, EMERGING MICROBES & INFECTIONS, Vol: 7, ISSN: 2222-1751
Wrench C, Belchamber KBR, Bercusson A, et al., 2018, Reduced Clearance of Fungal Spores by Chronic Obstructive Pulmonary Disease GM-CSF- and M-CSF-derived Macrophages, Publisher: AMER THORACIC SOC, Pages: 271-273, ISSN: 1044-1549
Armstrong-James D, de Boer L, Bercusson A, et al., 2018, From phagocytosis to metaforosis: Calcineurin's deadly role in innate processing of fungi, PLOS PATHOGENS, Vol: 14, ISSN: 1553-7366
Loss O, Bertuzzi M, Yan Y, et al., 2017, Mutual independence of alkaline- and calcium-mediated signalling in Aspergillus fumigatus refutes the existence of a conserved druggable signalling nexus, MOLECULAR MICROBIOLOGY, Vol: 106, Pages: 861-875, ISSN: 0950-382X
Armstrong-James D, Brown GD, Netea MG, et al., 2017, Immunotherapeutic approaches to treatment of fungal diseases., Lancet Infect Dis, Vol: 17, Pages: e393-e402
Fungal infections cause morbidity worldwide and are associated with an unacceptably high mortality despite the availability of antifungal drugs. The incidence of mycoses is rising because of the HIV pandemic and because immunomodulatory drugs are increasingly used to treat autoimmune diseases and cancer. New classes of antifungal drugs have only been partly successful in improving the prognosis for patients with fungal infection. Adjunctive host-directed therapy is therefore believed to be the only option to further improve patient outcomes. Recent advances in the understanding of complex interactions between fungi and host have led to the design and exploration of novel therapeutic strategies in cytokine therapy, vaccines, and cellular immunotherapy, each of which might become viable adjuncts to existing antifungal regimens. In this report, we discuss immunotherapeutic approaches-the rationale behind their design, the challenges in their use, and the progress that is so urgently needed to overcome the devastating effect of fungal diseases.
Abdolrasouli A, Armstrong-James D, Ryan L, et al., 2017, In vitro efficacy of disinfectants utilised for skin decolonisation and environmental decontamination during a hospital outbreak with Candida auris, MYCOSES, Vol: 60, Pages: 758-763, ISSN: 0933-7407
Rhodes J, Abdolrasouli A, Farrer R, et al., 2017, Rapid genome sequencing for outbreak analysis of the emerging human fungal pathogen Candida auris
Background: Candida auris was first described in 2009, and has since caused nosocomial outbreaks, invasive infections and fungaemia across 11 countries in five continents. An outbreak of C. auris occurred in a specialised cardiothoracic London hospital between April 2015 and November 2016, which to date has been the largest outbreak reported worldwide, involving a total of 72 patients. Methods: To understand the epidemiology of C. auris infection within this hospital, we sequenced the genomes of outbreak isolates using Oxford Nanopore Technologies and Illumina in order to type antifungal resistance alleles and to explore the outbreak within its local and global context. Findings: Phylogenomic analysis placed the UK outbreak in the India/Pakistan clade, demonstrating an Asian origin. The outbreak showed similar diversity to that of the entire clade and limited local spatiotemporal clustering was observed. One isolate displayed resistance to both echinocandins and 5-flucytosine; the former was associated with a serine to tyrosine amino acid substitution in the gene FKS1, and the latter was associated with a phenylalanine to isoleucine substitution in the gene FUR1. These mutations are novel for this pathogen. Interpretation: Multiple differential episodic selection of antifungal resistant genotypes has occurred within a genetically heterogenous population across this outbreak, creating a resilient pathogen and making it difficult to define local-scale patterns of transmission as well as implementing outbreak control measures. Funding: Antimicrobial Research Collaborative, Imperial College London
Amarsaikhan N, Sands EM, Shah A, et al., 2017, Caspofungin Increases Fungal Chitin and Eosinophil and γδ T Cell-Dependent Pathology in Invasive Aspergillosis., J Immunol, Vol: 199, Pages: 624-632
The polysaccharide-rich fungal cell wall provides pathogen-specific targets for antifungal therapy and distinct molecular patterns that stimulate protective or detrimental host immunity. The echinocandin antifungal caspofungin inhibits synthesis of cell wall β-1,3-glucan and is used for prophylactic therapy in immune-suppressed individuals. However, breakthrough infections with fungal pathogen Aspergillus fumigatus are associated with caspofungin prophylaxis. In this study, we report in vitro and in vivo increases in fungal surface chitin in A. fumigatus induced by caspofungin that was associated with airway eosinophil recruitment in neutropenic mice with invasive pulmonary aspergillosis (IA). More importantly, caspofungin treatment of mice with IA resulted in a pattern of increased fungal burden and severity of disease that was reversed in eosinophil-deficient mice. Additionally, the eosinophil granule proteins major basic protein and eosinophil peroxidase were more frequently detected in the bronchoalveolar lavage fluid of lung transplant patients diagnosed with IA that received caspofungin therapy when compared with azole-treated patients. Eosinophil recruitment and inhibition of fungal clearance in caspofungin-treated mice with IA required RAG1 expression and γδ T cells. These results identify an eosinophil-mediated mechanism for paradoxical caspofungin activity and support the future investigation of the potential of eosinophil or fungal chitin-targeted inhibition in the treatment of IA.
Armstrong-James D, Bicanic T, Brown GD, et al., 2017, AIDS-Related Mycoses: Current Progress in the Field and Future Priorities., Trends Microbiol, Vol: 25, Pages: 428-430
Opportunistic fungal infections continue to take an unacceptably heavy toll on the most disadvantaged living with HIV-AIDS, and are a major driver for HIV-related deaths. At the second EMBO Workshop on AIDS-Related Mycoses, clinicians and scientists from around the world reported current progress and key priorities for improving outcomes from HIV-related mycoses.
Cutino-Moguel M-T, Eades C, Rezvani K, et al., 2017, Immunotherapy for infectious diseases in haematological immunocompromise., Br J Haematol, Vol: 177, Pages: 348-356
Opportunistic infections remain a major problem across a broad spectrum of immunocompromised haematological patient groups, with viruses, bacteria, fungi and protozoa all presenting significant challenges. Given the major difficulties in treating many of these infections with the currently available antimicrobial chemotherapeutic arsenal, and the rapid emergence of antimicrobial resistance amongst all of the microbial kingdoms, novel strategies that enable host control or elimination of infection are urgently required. Recently, major progress has been made in our understanding of host immunocompromise in the haematological patient. In addition, a wide range of novel immunomodulatory strategies for infectious diseases have been developed. Here we discuss the major and wide-ranging areas of progress that have been made for host-directed immunotherapies in the context of infectious diseases, with relevance to haematological immunocompromise.
Alsuliman A, Muftuoglu M, Khoder A, et al., 2017, A subset of virus-specific CD161+ T cells selectively express the multidrug transporter MDR1 and are resistant to chemotherapy in AML., Blood, Vol: 129, Pages: 740-758
The establishment of long-lived pathogen-specific T cells is a fundamental property of the adaptive immune response. However, the mechanisms underlying long-term persistence of antigen-specific CD4+ T cells are not well-defined. Here we identify a subset of memory CD4+ T cells capable of effluxing cellular toxins, including rhodamine (Rho), through the multidrug efflux protein MDR1 (also known as P-glycoprotein and ABCB1). Drug-effluxing CD4+ T cells were characterized as CD161+CD95+CD45RA-CD127hiCD28+CD25int cells with a distinct chemokine profile and a Th1-polarized pro-inflammatory phenotype. CD4+CD161+Rho-effluxing T cells proliferated vigorously in response to stimulation with anti-CD3/CD28 beads and gave rise to CD161- progeny in vitro. These cells were also capable of self-renewal and maintained their phenotypic and functional characteristics when cultured with homeostatic cytokines. Multidrug-effluxing CD4+CD161+ T cells were enriched within the viral-specific Th1 repertoire of healthy donors and patients with acute myeloid leukemia (AML) and survived exposure to daunorubicin chemotherapy in vitro. Multidrug-effluxing CD4+CD161+ T cells also resisted chemotherapy-induced cytotoxicity in vivo and underwent significant expansion in AML patients rendered lymphopenic after chemotherapy, contributing to the repopulation of anti-CMV immunity. Finally, after influenza vaccination, the proportion of influenza-specific CD4+ T cells coexpressing CD161 was significantly higher after 2 years compared with 4 weeks after immunization, suggesting CD161 is a marker for long-lived antigen-specific memory T cells. These findings suggest that CD4+CD161+ T cells with rapid efflux capacity contribute to the maintenance of viral-specific memory T cells. These data provide novel insights into mechanisms that preserve antiviral immunity in patients undergoing chemotherapy and have implications for the development of novel immunotherapeutic approaches.
Bercusson A, de Boer L, Armstrong-James D, 2017, Endosomal sensing of fungi: current understanding and emerging concepts., Med Mycol, Vol: 55, Pages: 10-15
Endosomal sensing represents a key strategy by which mammalian cells detect parasitization by invading pathogens. This is critical for the control of fungal pathogens, which are for the most part phagocytosed by effector cells of the innate immune system. Despite rapid overall progress in our understanding of endosomal responses in recent times, relatively little is known about how the endosomal sensing system detects fungi and the ensuing immunological consequences. Considering that many fungal pathogens must overcome and evade endosomal killing in order to survive in the host, understanding this key area of the early innate response is crucial for our understanding of fungal infection. In this review we present a summary of our current knowledge of endosomal sensing within the context of fungal pathogens, with a focus on the myeloid compartment.
Shah A, Kannambath S, Herbst S, et al., 2016, Calcineurin Orchestrates Lateral Transfer of Aspergillus fumigatus during Macrophage Cell Death, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 194, Pages: 1127-1139, ISSN: 1073-449X
Schelenz S, Hagen F, Rhodes JL, et al., 2016, First hospital outbreak of the globally emerging Candida auris in a European hospital, ANTIMICROBIAL RESISTANCE AND INFECTION CONTROL, Vol: 5, ISSN: 2047-2994
Shah A, Armstrong-James D, 2016, Opportunist Turns Allergen: Double Life of Pneumocystis jirovecii in Asthma., Am J Respir Crit Care Med, Vol: 194, Pages: 779-780
Sekine T, Marin D, Cao K, et al., 2016, Specific combinations of donor and recipient KIR-HLA genotypes predict for large differences in outcome after cord blood transplantation, BLOOD, Vol: 128, Pages: 297-312, ISSN: 0006-4971
Bidula S, Sexton DW, Yates M, et al., 2015, H-ficolin binds Aspergillus fumigatus leading to activation of the lectin complement pathway and modulation of lung epithelial immune responses, IMMUNOLOGY, Vol: 146, Pages: 281-291, ISSN: 0019-2805
Corzo-León DE, Armstrong-James D, Denning DW, 2015, Burden of serious fungal infections in Mexico., Mycoses, Vol: 58 Suppl 5, Pages: 34-44
Serious fungal infections (SFIs) could be more frequent than are recognised. Estimates of the incidence and prevalence of SFIs are essential in order to identify public health problems. We estimated the rates of SFIs in Mexico, following a methodology similar to that used in prior studies. We obtained information about the general population and populations at risk. A systematic literature search was undertaken to identify epidemiological reports of SFIs in Mexico. When Mexican reports were unavailable, we based our estimates on international literature. The most prevalent SFIs in Mexico are recurrent vulvovaginal candidiasis (5999 per 100,000) followed by allergic bronchopulmonary aspergillosis (60 per 100,000), chronic pulmonary aspergillosis (15.9 per 100,000), fungal keratitis (10.4 per 100,000), invasive candidiasis (8.6 per 100,000) and SFIs in HIV (8.2 per 100,000); coccidioidomycosis (7.6 per 100,000), IA (4.56 per 100,000). These correspond to 2,749,159 people affected in any year (2.45% of the population), probably >10,000 deaths and 7000 blind eyes. SFIs affect immunocompromised and healthy populations. Most are associated with high morbidity and mortality rates. Validation of these estimates with epidemiological studies is required. The burdens indicate that an urgent need to improve medical skills, surveillance, diagnosis, and management of SFIs exists.
Tanaka RJ, Boon NJ, Vrcelj K, et al., 2015, In silico modeling of spore inhalation reveals fungal persistence following low dose exposure, SCIENTIFIC REPORTS, Vol: 5, ISSN: 2045-2322
Bidula S, Sexton DW, Abdolrasouli A, et al., 2015, The Serum Opsonin L-ficolin Is Detected in Lungs of Human Transplant Recipients Following Fungal Infections and Modulates Inflammation and Killing of Aspergillus fumigatus, JOURNAL OF INFECTIOUS DISEASES, Vol: 212, Pages: 234-246, ISSN: 0022-1899
Shirkhani K, Teo I, Armstrong-James D, et al., 2015, Nebulised amphotericin B-polymethacrylic acid nanoparticle prophylaxis prevents invasive aspergillosis, NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE, Vol: 11, Pages: 1217-1226, ISSN: 1549-9634
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