What makes Aspergillus fumigatus a successful pathogen? Genes and molecules involved in invasive aspergillosis

Abad, Ana; Fernandez-Molina, Jimena V.; Bikandi, Joseba; Ramírez, Amaia; Margareto, Javier; Sendino, Javier; Hernando, Fernando; Pontón, José; Garaizar, Javier; Rementerı́a, Aitor

doi:10.1016/j.riam.2010.10.003

Cited by 354 publications

(309 citation statements)

References 290 publications

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“…To promote its survival, A. fumigatus is able to impair its host's immune responses by secreting mycotoxins such as gliotoxins (59). These toxins are known to inhibit phagocytosis and induce apoptosis of monocytes and neutrophils (60,61).…”

Section: Discussionmentioning

confidence: 99%

A Polysaccharide Virulence Factor of a Human Fungal Pathogen Induces Neutrophil Apoptosis via NK Cells

Robinet

Baychelier

Fontaine

et al. 2014

The Journal of Immunology

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Aspergillus fumigatus is an opportunistic human fungal pathogen that sheds galactosaminogalactan (GG) into the environment. Polymorphonuclear neutrophils (PMNs) and NK cells are both part of the first line of defense against pathogens. We recently reported that GG induces PMN apoptosis. In this study, we show that PMN apoptosis occurs via a new NK cell–dependent mechanism. Reactive oxygen species, induced by the presence of GG, play an indispensable role in this apoptotic effect by increasing MHC class I chain–related molecule A expression at the PMN surface. This increased expression enables interaction between MHC class I chain–related molecule A and NKG2D, leading to NK cell activation, which in turn generates a Fas-dependent apoptosis-promoting signal in PMNs. Taken together, our results demonstrate that the crosstalk between PMNs and NK cells is essential to GG-induced PMN apoptosis. NK cells might thus play a role in the induction of PMN apoptosis in situations such as unexplained neutropenia or autoimmune diseases.

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Section: Discussionmentioning

confidence: 99%

A Polysaccharide Virulence Factor of a Human Fungal Pathogen Induces Neutrophil Apoptosis via NK Cells

Robinet

Baychelier

Fontaine

et al. 2014

The Journal of Immunology

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“…[1][2][3] While A. fumigatus is the most commonly cause of IA worldwide, A. terreus appears to be frequently isolated in some institutions; e.g. the Medical University Hospital of Innsbruck, Austria, where approximately 15% of all Aspergillus infections are caused by this pathogen, and the M.D.…”

Section: Introductionmentioning

confidence: 99%

Galleria mellonellaas a host model to studyAspergillus terreusvirulence and amphotericin B resistance

et al. 2015

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Keywords: amphotericin B resistant and susceptible A. terreus strain cluster, Galleria mellonella, invertebrate in vivo modelThe aim of this study was to investigate if the alternative in vivo model Galleria mellonella can be used (i) to determine differences in pathogenicity of amphotericin B (AMB) resistant and susceptible A. terreus isolates, (ii) to evaluate AMB efficacy in vivo (iii) and to correlate outcome to in vitro susceptibility data. Larvae were infected with 2 A. terreus AMB resistant (ATR) and 3 AMB susceptible (ATS) isolates and survival rates were correlated to physiological attributes and killing ability of larval haemocytes. Additionally, infected larvae were treated with different concentrations of L-AMB. Haemocyte density were ascertained to evaluate the influence of L-AMB on the larval immune cells. Larvae were sensitive to A. terreus infection in an inoculum-size and temperature dependent manner. In vitro susceptibility to L-AMB correlated with in vivo outcome of antifungal treatment, defining an AMB susceptible strain cluster of A. terreus. Susceptibility to L-AMB increased virulence potential in the larval model, but this increase was also in accordance with faster growth and less damage caused by larval haemocytes. L-AMB treatment primed the larval immune response by increasing haemocyte density. G. mellonella provides a convenient model for the in vivo screening of A. terreus virulence and treatment options, contributing to the generation of a hypothesis that can be further tested in refined experiments in mammalian models.

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“…Invasive aspergillosis is the most common invasive mold infection of humans, with the species A. fumigatus accounting for the majority of these infections (reviewed in Abad et al 2010). Both conidia and hyphae of A. fumigatus interact with a number of pulmonary cell types during different stages of invasive aspergillosis.…”

Section: A Fumigatusmentioning

confidence: 99%

Host Cell Invasion by Medically Important Fungi

Sheppard

Filler

2014

Cold Spring Harbor Perspectives in Medicine

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What makes Aspergillus fumigatus a successful pathogen? Genes and molecules involved in invasive aspergillosis

Cited by 354 publications

References 290 publications

A Polysaccharide Virulence Factor of a Human Fungal Pathogen Induces Neutrophil Apoptosis via NK Cells

A Polysaccharide Virulence Factor of a Human Fungal Pathogen Induces Neutrophil Apoptosis via NK Cells

Galleria mellonellaas a host model to studyAspergillus terreusvirulence and amphotericin B resistance

Host Cell Invasion by Medically Important Fungi

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