Fulminant Mulch Pneumonitis: An Emergency Presentation of Chronic Granulomatous Disease

Siddiqui, Sophia; Anderson, Victoria; Hilligoss, Diane; Abinun, Mario; Kuijpers, Taco W.; Masur, Henry; Witebsky, Frank G.; Shea, Yvonne R.; Gallin, John I.; Malech, Harry L.; Holland, Steven M.

doi:10.1086/520985

Cited by 147 publications

(103 citation statements)

References 30 publications

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“…Besides impaired phagocyte oxidative killing, exuberant inflammatory responses to fungal particles have also been implicated in the pathogenesis of IA in CGD (Morgenstern et al 1997;Romani et al 2008). In fact, inhalation of aerosolized decayed organic matter in mulch or hay can cause fulminant Aspergillus pneumonitis, known as "mulch pneumonitis," a combined hypersensitivity and IA syndrome, for which prompt corticosteroid and antifungal drug administration is imperative for good clinical response (Siddiqui et al 2007). Similar to immunosuppressed patients at risk for IA, Aspergillus fumigatus is the most common species, but Aspergillus nidulans is encountered almost exclusively in CGD, for reasons that remain unknown, and is distinctive because of its resistance to antifungals and its propensity to invade contiguous anatomical planes (Segal et al 1998).…”

Section: Disorders Of the Phagocyte Oxidative Burst Machinerymentioning

confidence: 99%

Mendelian Genetics of Human Susceptibility to Fungal Infection

Lionakis

Netea

Holland

2014

Cold Spring Harbor Perspectives in Medicine

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Correspondence: lionakism@niaid.nih.gov A recent surge in newly described inborn errors of immune function-related genes that result in susceptibility to fungal disease has greatly enhanced our understanding of the cellular and molecular basis of antifungal immune responses. Characterization of single-gene defects that predispose to various combinations of superficial and deep-seated infections caused by yeasts, molds, and dimorphic fungi has unmasked the critical role of novel molecules and signaling pathways in mucosal and systemic antifungal host defense. These experiments of nature offer a unique opportunity for developing new knowledge in immunological research and form the foundation for devising immune-based therapeutic approaches for patients infected with fungal pathogens.

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Section: Disorders Of the Phagocyte Oxidative Burst Machinerymentioning

confidence: 99%

Mendelian Genetics of Human Susceptibility to Fungal Infection

Lionakis

Netea

Holland

2014

Cold Spring Harbor Perspectives in Medicine

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“…The large amounts of superoxide produced by the membrane-associated NADPH oxidase in neutrophils have a central role in the destruction of invading pathogens as well as in the resolution of inflammation. [5][6][7][8][9] Congenital defects that prevent NADPH oxidase activity result in chronic granulomatous disease (CGD), which is characterized by exaggerated immune responses 10 and recurrent life-threatening infections by a narrow set of microorganisms. 11 We recently found that formation of NETs by activated neutrophils requires not only NADPH-oxidasemediated superoxide production, but also autophagy.…”

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confidence: 99%

Dying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality

et al. 2011

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Neutrophil extracellular traps (NETs) are chromatin structures loaded with antimicrobial molecules. They can trap and kill various bacterial, fungal and protozoal pathogens, and their release is one of the first lines of defense against pathogens. In vivo, NETs are released during a form of pathogen-induced cell death, which was recently named NETosis. Ex vivo, both dead and viable neutrophils can be stimulated to release NETs composed of either nuclear or mitochondrial chromatin, respectively. In certain pathological conditions, NETs are associated with severe tissue damage or certain auto-immune diseases. This review describes the recent progress made in the identification of the mechanisms involved in NETosis and discusses its interplay with autophagy and apoptosis. Cell Death and Differentiation (2011) 18, 581-588; doi:10.1038/cdd.2011.1; published online 4 February 2011Neutrophils have an essential role in innate immunity and are the first cells recruited to the site of infection.1 Human neutrophils are the most abundant leukocytes. They have a very short lifespan, and neutrophil homeostasis is maintained by continuous release of many neutrophils from the bone marrow. Accelerated neutrophil death decreases neutrophil counts (neutropenia) and increases susceptibility to infection. In turn, delayed neutrophil death increases neutrophil counts (neutrophilia) and intensifies innate defenses, possibly promoting chronic inflammation.2 Neutrophils perform their function by engulfing microorganisms or opsonized particles and degrading them by various molecules, and also release lytic enzymes that destroy extracellular pathogens.3 Moreover, they release structures called neutrophil extracellular traps (NETs) that can trap and kill microbes. 4 The neutrophil lifespan constitutes a sensitive balance between their function as effecter cells and their potential to inflict tissue damage. In the absence of inflammatory stimuli, neutrophils continuously undergo apoptosis within 24-48 h both in vivo and in cell culture. The large amounts of superoxide produced by the membrane-associated NADPH oxidase in neutrophils have a central role in the destruction of invading pathogens as well as in the resolution of inflammation. [5][6][7][8][9] Congenital defects that prevent NADPH oxidase activity result in chronic granulomatous disease (CGD), which is characterized by exaggerated immune responses 10 and recurrent life-threatening infections by a narrow set of microorganisms. 11 We recently found that formation of NETs by activated neutrophils requires not only NADPH-oxidasemediated superoxide production, but also autophagy. 12In this review, we present an overview of the main biochemical and morphological features observed during neutrophil activation and discuss in more detail the contribution of NADPH oxidase, histone citrullination, intracellular calcium levels and autophagy to chromatin decondensation and NET formation. Release of Extracellular TrapsIn 2004, the group of Brinkman and Zychlinsky was the first to report the rele...

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“…Cependant, au niveau clinique et radiologique, l'extension pariétale thoracique d'une infection pulmonaire (masse médiasti-nale, atteinte de la paroi thoracique ou du diaphragme) est particulièrement fréquente lors d'infections fongiques invasives chez les patients atteints de CGD [15]. Une entité clinique exclusivement associée à la CGD, la pneumonie de la paille ou mulch pneumonitis, a récem-ment été décrite chez neuf patients [24]. Elle se caractérise par des infiltrats diffus (plutôt que des nodules) chez des patients CGD qui, tous, ont une histoire d'exposition récente à des végétaux, notamment à la la peau [19].…”

Section: Physiopathologie Des Infections Fongiques Au Cours De La Cgdunclassified

Infections fongiques et granulomatose septique chronique

et al. 2012

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> La granulomatose septique chronique est une maladie héréditaire liée à un dysfonctionnement de la NADPH oxydase des cellules phagocytaires. Ce désordre entraîne une inactivation intracellulaire anormale des microorganismes, principalement des champignons tels que Aspergillus spp. et d'autres espèces moins fréquemment isolées ou émergentes. Nous proposons ici une synthèse des bases génétiques, de la physiopathologie et de la présentation clinique des infections fongiques invasives dans la granulomatose septique chronique, et nous évoquons les stratégies thé-rapeutiques préventives et curatives disponibles à ce jour. < Les bases génétiques de la CGDLes mécanismes physiopathologiques impliqués dans la CGD ont été décrits initialement par Segal et Jones [1]. Le complexe NADPH oxydase activé est responsable de l'explosion oxydative (une consommation rapide d'oxygène) qui survient en réponse à la stimulation des polynucléaires neutrophiles. Il comprend cinq sousunités (Figure 1) composées de glycoprotéines nommées en fonction de leurs poids moléculaires et qui associent deux composantes : le flavocytochrome b-245 (comprenant 91kD glycoprotein of phagocyte oxidase [gp91phox] et p22phox) situé dans la membrane du phagosome, et les trois protéines p47phox, p67phox et p40phox, au niveau du cytosol. Le noyau catalytique de la NADPH oxydase des cellules phagocytaires est gp91phox, maintenant renommée Nox2. Gp91phox/Nox2 forme une structure qui permet le transport des électrons de la NADPH du cytoplasme cellulaire, via la flavine adénine dinucléotide (FAD) et les deux

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Fulminant Mulch Pneumonitis: An Emergency Presentation of Chronic Granulomatous Disease

Cited by 147 publications

References 30 publications

Mendelian Genetics of Human Susceptibility to Fungal Infection

Mendelian Genetics of Human Susceptibility to Fungal Infection

Dying for a cause: NETosis, mechanisms behind an antimicrobial cell death modality

Infections fongiques et granulomatose septique chronique

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