Murine Intraepithelial Dendritic Cells Interact With Phagocytic Cells During Aspergillus fumigatus-Induced Inflammation

Bogorodskiy, Andrey; Bolkhovitina, Elena L; Gensch, Thomas; Troyanova, Natalia I; Mishin, Alexey; Okhrimenko, Ivan; Braun, Armin; Spies, Emma; Gordeliy, Valentin; Sapozhnikov, Alexander M.; Borshchevskiy, Valentin; Shevchenko, Marina

doi:10.3389/fimmu.2020.00298

Cited by 5 publications

(3 citation statements)

References 46 publications

(68 reference statements)

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“…Moreover, tissue fixation is necessary, and, therefore, the analyses are limited to acquisition of the single time points of the infection process. While able to rapidly image whole organs, LSFM has a lower spatial resolution than confocal laser-scanning microscopy, which has been recently used by Bogorodskiy et al (2020) to look at the behaviour of intra-epithelial dendritic cells during A. fumigatus infections [ 40 , 41 ]. This methodology uses a similar lung clearing procedure to that in Amich et al (2020) but coarsely sections the lung into thick slices to visualise the host–pathogen interactions.…”

Section: Are a Fumigatus Spores Deposited In The A...mentioning

confidence: 99%

Novel Insights into Aspergillus fumigatus Pathogenesis and Host Response from State-of-the-Art Imaging of Host–Pathogen Interactions during Infection

Ortiz

Pennington

Thomson

et al. 2022

JoF

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Aspergillus fumigatus spores initiate more than 3,000,000 chronic and 300,000 invasive diseases annually, worldwide. Depending on the immune status of the host, inhalation of these spores can lead to a broad spectrum of disease, including invasive aspergillosis, which carries a 50% mortality rate overall; however, this mortality rate increases substantially if the infection is caused by azole-resistant strains or diagnosis is delayed or missed. Increasing resistance to existing antifungal treatments is becoming a major concern; for example, resistance to azoles (the first-line available oral drug against Aspergillus species) has risen by 40% since 2006. Despite high morbidity and mortality, the lack of an in-depth understanding of A. fumigatus pathogenesis and host response has hampered the development of novel therapeutic strategies for the clinical management of fungal infections. Recent advances in sample preparation, infection models and imaging techniques applied in vivo have addressed important gaps in fungal research, whilst questioning existing paradigms. This review highlights the successes and further potential of these recent technologies in understanding the host–pathogen interactions that lead to aspergillosis.

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Section: Are a Fumigatus Spores Deposited In The A...mentioning

confidence: 99%

Novel Insights into Aspergillus fumigatus Pathogenesis and Host Response from State-of-the-Art Imaging of Host–Pathogen Interactions during Infection

Ortiz

Pennington

Thomson

et al. 2022

JoF

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“…Previously, we demonstrated that upon inflammation, in the conducting airway mucosa, CD11b + cells were mostly represented by the Ly6G + neutrophils (Bogorodskiy et al, 2020). Thus, our present data support the evidence that FluoSpheres suspended in RBD solution (rather than a phosphate buffer) can attract neutrophils to the conducting airway mucosa and facilitate the ingestion activity of these neutrophils.…”

Section: Resultsmentioning

confidence: 97%

The SARS-CoV-2 receptor-binding domain facilitates neutrophil transepithelial migration and nanoparticle uptake in the mice airways

Bolkhovitina

Vavilova

Bogorodskiy

et al. 2022

Preprint

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SARS-CoV-2-induced infection is still dangerous. Mouse models are convenient to the investigation of virus-activated immune response mechanisms. However, mice are not proper model organisms to study COVID-19 due to decreased interaction affinity between the SARS-CoV-2 receptor-binding domain (RBD) and mouse angiotensin-converting enzyme 2 (ACE2) compared with human ACE2. In the present study, we propose a mouse model that allows estimating the influence of SARS-CoV-2 on the immune system. To mimic the effects of RBD-ACE2 high-affinity interaction, mice received the ACE2 inhibitor MLN-4760. To simulate virus loading, we applied 100 nm particles suspended in the solution of RBD via the oropharyngeal route to mice. In this model, MLN-4760 application enhanced neutrophil egress from the bone marrow to the bloodstream and RBD attracted neutrophils to the luminal side of the conducting airway epithelium. By contrast, inert 100 nm particles were not potent to stimulate neutrophil recruitment to the conducting airway mucosa. Using this model, and by altering the dosage of the ACE2 inhibitor, nanoparticles, and RBD, one can adapt it to investigate different COVID-19 states characterized with mild or severe airway inflammation.

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“…Transfer of A. fumigatus -pulsed DCs into naive mice has been shown to confer protective Th1 CD4+ T cell responses secreting interferon (IFN)-γ during A. fumigatus infection which decreased fungal burden and enhanced survival [ 298 ]. On the other hand, cDCs may also dampen excessive anti- A. fumigatus immunity, with one study suggesting that lung intraepithelial DCs inhibit clustering of CD11b+ neutrophils via increased efferocytosis of apoptotic neutrophils which accumulate in the lungs, which would help prevent excessive neutrophilic inflammation and subsequent tissue damage [ 299 ]. Ultimately, the discovery of more subsets of cDC1s and cDC2s may give further mechanistic insight into their role in invasive aspergillosis and provide an understanding of how cDCs play opposing roles in promoting Th1 or Th17 inflammation.…”

Section: Interactions Of a Fumigatus With Host Imm...mentioning

confidence: 99%

Pathogenicity and virulence of Aspergillus fumigatus

et al. 2023

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Pulmonary infections caused by the mould pathogen Aspergillus fumigatus are a major cause of morbidity and mortality globally. Compromised lung defences arising from immunosuppression, chronic respiratory conditions or more recently, concomitant viral or bacterial pulmonary infections are recognised risks factors for the development of pulmonary aspergillosis. In this review, we will summarise our current knowledge of the mechanistic basis of pulmonary aspergillosis with a focus on emerging at-risk populations.

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Murine Intraepithelial Dendritic Cells Interact With Phagocytic Cells During Aspergillus fumigatus-Induced Inflammation

Cited by 5 publications

References 46 publications

Novel Insights into Aspergillus fumigatus Pathogenesis and Host Response from State-of-the-Art Imaging of Host–Pathogen Interactions during Infection

Novel Insights into Aspergillus fumigatus Pathogenesis and Host Response from State-of-the-Art Imaging of Host–Pathogen Interactions during Infection

The SARS-CoV-2 receptor-binding domain facilitates neutrophil transepithelial migration and nanoparticle uptake in the mice airways

Pathogenicity and virulence of Aspergillus fumigatus

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