Interaction of airway epithelial cells (A549) with spores and mycelium of Aspergillus fumigatus

Zhang, Zhihong; Liu, Rong‐Yu; Noordhoek, Jacobien A.; Kauffman, Henk F.

doi:10.1016/j.jinf.2004.12.012

Cited by 61 publications

(54 citation statements)

References 38 publications

(42 reference statements)

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“…In addition, exposure to inactivated A. fumigatus conidia did not induce any significant modifications of the mRNA levels of the factors studied. Similar results for cytokine production using ELISA were obtained using non-viable fragments of mycelium and inactivated A. fumigatus conidia (Zhang et al, 2005). Recently, infection with hyphae, but not with conidia, was shown to stimulate endothelial cells to synthesize IL-8 and TNF-a in vitro using ELISA (Chiang et al, 2008).…”

Section: Mrna Quantificationsupporting

confidence: 61%

“…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 often more allergenic (Kauffman et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…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 Abbreviations: ANOVA, analysis of variance; C t , cycle threshold; GM-CSF, granulocyte-monocyte colony-stimulating factor; IL, interleukin; IPA, invasive pulmonary aspergillosis; TNF, tumour necrosis factor.…”

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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: Mrna Quantificationsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

mentioning

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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“…Upon challenge by A. fumigatus, a number of cytokines, including IL-5, IL-6, IL-8, IL-13, and gamma interferon (IFN-␥), and the chemokine monocyte chemotactic protein-1 (MCP-1) have been observed to be induced (46)(47)(48). The role of opsonins in cytokine activation has also been acknowledged, with surfactant protein-D eliciting cytokine responses from A549 cells in response to allergens (49).…”

Section: Discussionmentioning

confidence: 99%

Role of Ficolin-A and Lectin Complement Pathway in the Innate Defense against Pathogenic Aspergillus Species

et al. 2013

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Aspergillus species are saprophytic molds causing life-threatening invasive fungal infections in the immunocompromised host. Innate immune recognition, in particular, the mechanisms of opsonization and complement activation, has been reported to be an integral part of the defense against fungi. We have shown that the complement component ficolin-A significantly binds to Aspergillus conidia and hyphae in a concentration-dependent manner and was inhibited by N-acetylglucosamine and N-acetylgalactosamine. Calcium-independent binding to Aspergillus fumigatus and A. terreus was observed, but binding to A. flavus and A. niger was calcium dependent. Ficolin-A binding to conidia was increased under low-pH conditions, and opsonization led to enhanced binding of conidia to A549 airway epithelial cells. In investigations of the lectin pathway of complement activation, ficolin-A-opsonized conidia did not lead to lectin pathway-specific C4 deposition. In contrast, the collectin mannose binding lectin C (MBL-C) but not MBL-A led to efficient lectin pathway activation on A. fumigatus in the absence of ficolin-A. In addition, ficolin-A opsonization led to a modulation of the proinflammatory cytokine interleukin-8. We conclude that ficolin-A may play an important role in the innate defense against Aspergillus by opsonizing conidia, immobilizing this fungus through enhanced adherence to epithelial cells and modulation of inflammation. However, it appears that other immune pattern recognition molecules, i.e., those of the collectin MBL-C, are involved in the Aspergillus-lectin complement pathway activation rather than ficolin-A.

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“…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). Recent studies of a human bronchial epithelial cell line (BEAS-2B) have also demonstrated a time-dependent synthesis of CXCL8 in response to germinated Aspergillus elements (swollen conidia, hyphae, or both) but not resting conidia (9).…”

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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Interaction of airway epithelial cells (A549) with spores and mycelium of Aspergillus fumigatus

Cited by 61 publications

References 38 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

Role of Ficolin-A and Lectin Complement Pathway in the Innate Defense against Pathogenic Aspergillus Species

Innate Immunity toAspergillusSpecies

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