Phagocytosis of Aspergillus fumigatus conidia by primary nasal epithelial cells in vitro

Botterel, Françoise; Gross, Karine; Ibrahim-Granet, Oumaïma; Khoufache, Khaled; Escabasse, Virginie; Coste, A.; Cordonnier, Catherine; Escudier, Estelle; Bretagne, Stéphane

doi:10.1186/1471-2180-8-97

Cited by 61 publications

(69 citation statements)

References 27 publications

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“…The internalized conidia were quantified using the fluorescence brightener Blankophor-P-fluessig [4,49-bis[(4-anilino-6-substituted-1,3,5-trazine-2-yl) amino stilbene-2,29-disulfonic acid], kindly provided by Bayer (Botterel et al, 2008).…”

Section: Methodsmentioning

confidence: 99%

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Aspergillus fumigatus germ tube growth and not conidia ingestion induces expression of inflammatory mediator genes in the human lung epithelial cell line A549

Bellanger

Millon

Khoufache

et al. 2009

Journal of Medical Microbiology

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Inhalation of conidia is the main cause of invasive pulmonary aspergillosis (IPA) and the respiratory epithelium is the first line of defence. To explore the triggering factor for the inflammatory response to Aspergillus fumigatus, the species mainly responsible for IPA, this study analysed the differential expression of three inflammatory genes in A549 cells after challenge with live and killed conidia. The influence of steroids, one of the main risk factors for developing IPA, was also investigated. Quantification of mRNAs of the inflammatory mediator genes encoding interleukin (IL)-8, tumour necrosis factor (TNF)-a and granulocyte-monocyte colony-stimulating factor (GM-CSF) was carried out using real-time PCR. Ingestion rates were studied for the conidia of A. fumigatus and Penicillium chrysogenum using a fluorescence brightener. Similar results were obtained for both species, with ingestion rates ranging from 35 to 40 %. Exposure of A549 cells to live A. fumigatus conidia only induced a four-to fivefold increase in the mRNA levels of the three genes, starting 8 h after the initial contact. Both inactivation of live A. fumigatus conidia and treatment by dexamethasone (10 "7 M) prevented the overexpression of TNF-a, IL-8 and GM-CSF. Fungal growth, rather than conidia ingestion, appears to be the main stimulus for the production of inflammatory mediators by epithelial cells, and this production is inhibited by steroid therapy. These results underline the role that the epithelium plays in the innate response against IPA. INTRODUCTIONInvasive pulmonary aspergillosis (IPA) is an opportunistic infection whose incidence is increasing at the same rate as the number of severely immunocompromised patients (Lin et al., 2001). Neutropenia and high-dose steroid treatments are the main risk factors for IPA, and these underline the importance of an appropriate inflammatory response if fungal invasion is to be avoided. Most authors stress the important roles that alveolar macrophages and neutrophils play in controlling infection (Romani, 2004;Walsh et al., 2005). The release of innate immune-related molecules from professional phagocytic cells in the course of Aspergillus fumigatus infection has been widely studied (Meier et al., 2003;Pylkkanen et al., 2004;Cortez et al., 2006). However, the respiratory epithelium is the first tissue that inhaled conidia encounter, and it probably participates in the efficient coordinated response against IPA. In animal models of IPA, most inhaled conidia are trapped in the upper respiratory tract, and the respiratory epithelium coordinates with alveolar macrophages (Stephens-Romero et al., 2005).A few studies have investigated the production of inflammatory mediators by studying the human lung epithelial cell line A549 after stimulation with moulds or mould extracts (Borger et al., 1999; Kauffman et al., 2000; Huttunen et al., 2003;Zhang et al., 2005; Tai et al., 2006). These studies have focused on fungi as the source of allergens, and on species other than A. fumigatus, which are Abbrevi...

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Section: Methodsmentioning

confidence: 99%

“…We used in our study Penicillium chrysogenum as a control for conidia ingestion (Botterel et al, 2008). P. chrysogenum is a mould that is highly predominant in the environment, with a conidial size (3-4 mm diameter) similar to that of A. fumigatus.…”

Section: Introductionmentioning

confidence: 99%

Aspergillus fumigatus germ tube growth and not conidia ingestion induces expression of inflammatory mediator genes in the human lung epithelial cell line A549

Bellanger

Millon

Khoufache

et al. 2009

Journal of Medical Microbiology

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“…More recently, an in vitro study has shown that PAR 2 activation on monocytes enhanced the suppressive effects of IFN-␥ on IAV replication (21). The role of PAR 2 activation in other cell types and particularly in epithelial cells, one of the primary cell types exposed to different pathogens and to IAV (22,23), has never been studied in the context of viral infection. Furthermore, the specific role of PAR 2 activation in in vivo in models of viral infection has never been addressed.…”

Section: Nfluenza Virus Type a (Iav)mentioning

confidence: 99%

Protective Role for Protease-Activated Receptor-2 against Influenza Virus Pathogenesis via an IFN-γ-Dependent Pathway

Khoufache

LeBouder

Morello

et al. 2009

The Journal of Immunology

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Protease-activated receptor-2 (PAR2), a receptor highly expressed in the respiratory tract, can influence inflammation at mucosal surfaces. Although the effects of PAR2 in the innate immune response to bacterial infection have been documented, knowledge of its role in the context of viral infection is lacking. We thus investigated the role of PAR2 in influenza pathogenesis in vitro and in vivo. In vitro, stimulation of PAR2 on epithelial cells inhibited influenza virus type A (IAV) replication through the production of IFN-γ. In vivo, stimulation of PAR2 using specific agonists protected mice from IAV-induced acute lung injury and death. This effect correlated with an increased clearance of IAV in the lungs associated with increased IFN- γ production and a decreased presence of neutrophils and RANTES release in bronchoalveolar fluids. More importantly, the protective effect of the PAR2 agonist was totally abrogated in IFN- γ-deficient mice. Finally, compared with wild-type mice, PAR2-deficient mice were more susceptible to IAV infection and displayed more severe lung inflammation. In these mice higher neutrophil counts and increased RANTES concentration but decreased IFN- γ levels were observed in the bronchoalveolar lavages. Collectively, these results showed that PAR2 plays a protective role during IAV infection through IFN-γ production and decreased excessive recruitment of inflammatory cells to lung alveoli.

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“…3). Similarly, human nasal ciliated epithelial cells phagocytose and kill conidia in vitro (20). A human alveolar epithelial cell line (A549) can bind both Aspergillus conidia and hyphae, ingest conidia, and generate IL-6 and CXCL8 in response to them (75,177).…”

Section: Epithelial Cellsmentioning

confidence: 99%

Innate Immunity toAspergillusSpecies

Park¹,

2009

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SUMMARY All humans are continuously exposed to inhaled Aspergillus conidia, yet healthy hosts clear the organism without developing disease and without the development of antibody- or cell-mediated acquired immunity to this organism. This suggests that for most healthy humans, innate immunity is sufficient to clear the organism. A failure of these defenses results in a uniquely diverse set of illnesses caused by Aspergillus species, which includes diseases caused by the colonization of the respiratory tract, invasive infection, and hypersensitivity. A key concept in immune responses to Aspergillus species is that the susceptibilities of the host determine the morphological form, antigenic structure, and physical location of the fungus. In this review, we summarize the current literature on the multiple layers of innate defenses against Aspergillus species that dictate the outcome of this host-microbe interaction.

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Phagocytosis of Aspergillus fumigatus conidia by primary nasal epithelial cells in vitro

Cited by 61 publications

References 27 publications

Aspergillus fumigatus germ tube growth and not conidia ingestion induces expression of inflammatory mediator genes in the human lung epithelial cell line A549

Aspergillus fumigatus germ tube growth and not conidia ingestion induces expression of inflammatory mediator genes in the human lung epithelial cell line A549

Protective Role for Protease-Activated Receptor-2 against Influenza Virus Pathogenesis via an IFN-γ-Dependent Pathway

Innate Immunity toAspergillusSpecies

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