Binding and Germination of Aspergillus fumigatus Conidia on Cultured A549 Pneumocytes

DeHart, Del J.; Agwu, David E.; Julian, N.C.; Washburn, Ronald G.

doi:10.1093/infdis/175.1.146

Cited by 77 publications

(63 citation statements)

References 18 publications

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“…Previous research has highlighted that L-ficolin is able to function as an opsonin and enhance phagocytosis of S. Typhimurium and S. agalactiae (14,15). Due to the small size of the conidia, they can penetrate deep into the lungs, where they initially encounter the lung epithelium, in particular, type II pneumocytes (35). Ficolin-A mRNA has been observed to be most highly expressed in the liver and spleen; however, ficolin-A mRNA has also been observed to be expressed in the lung, suggesting the potential for its role in lung defense (36).…”

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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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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“…For monocytes and macrophages, a mannosyl-fucosyl receptor (39) and receptors inhibited by glucan and chitooligosaccharides (40) have been described. Conidial binding to pneumocytes was instead glycosphingolipid-mediated (41).…”

Section: Discussionmentioning

confidence: 99%

Dendritic Cells Transport Conidia and Hyphae ofAspergillus fumigatusfrom the Airways to the Draining Lymph Nodes and Initiate Disparate Th Responses to the Fungus

Bozza

Gaziano

Spreca

et al. 2002

The Journal of Immunology

308

284

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Aspergilli are respiratory pathogens and pulmonary infections are usually acquired through the inhalation of conidia, able to reach small airways and the alveolar space where the impaired host defense mechanisms allow hyphal germination and subsequent tissue invasion. The invasive pulmonary aspergillosis is the most common manifestation of Aspergillus fumigatus infection in immunocompromised patients and is characterized by hyphal invasion and destruction of pulmonary tissue. A Th1/Th2 dysregulation and a switch to a Th2 immune response may contribute to the development and unfavorable outcome of invasive pulmonary aspergillosis. Dendritic cells (DC) have a primary role in surveillance for pathogens at the mucosal surfaces and are recognized as the initiators of immune responses to them. In the present study, we assessed the functional activity of pulmonary DC in response to A. fumigatus conidia and hyphae, both in vitro and in vivo. We analyzed mechanisms and receptors for phagocytosis by DC as well as DC migration, maturation, and Th priming in vivo upon exposure to either form of the fungus. We found a remarkable functional plasticity of DC in response to the different forms of the fungus, as pulmonary DC were able to: 1) internalize conidia and hyphae of A. fumigatus through distinct phagocytic mechanisms and recognition receptors; 2) discriminate between the different forms in terms of cytokine production; 3) undergo functional maturation upon migration to the draining lymph nodes and spleens; and 4) instruct local and peripheral Th cell reactivity to the fungus.

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“…Previous work by our laboratory and others has determined that A. fumigatus conidia are internalized by lung cells (DeHart et al, 1997;Paris et al, 1997;Wasylnka and Moore, 2002) endothelial cells (Paris et al, 1997;Wasylnka and Moore, 2002) and macrophages (Nessa et al, 1997;Wasylnka and Moore, 2002) in vitro. We have previously demonstrated that 100% of conidia internalized by A549 lung epithelial cells survive for at least 3 1/2 hours following uptake, whereas 70% of conidia internalized by J774 murine macrophages are killed within 6 hours.…”

Section: Introductionmentioning

confidence: 88%

Aspergillus fumigatus conidia survive and germinate in acidic organelles of A549 epithelial cells

Wasylnka

Moore

2003

Journal of Cell Science

145

150

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Aspergillus fumigatus is an environmental mould that can cause invasive disease in the immunocompromised host. Previous work has shown that conidia can be internalized by lung epithelial cells (A549) and murine macrophages (J774) in vitro. Therefore, the purpose of this study was to determine the fate of A. fumigatus conidia within the endosomal network of these cells. Co-localization of conidia expressing green fluorescent protein with proteins present in the early endosomal (CD71) and lysosomal (CD63, LAMP-1) membrane was assessed using confocal microscopy. In J774 cells, 75% of internalized conidia were found in phagosomes containing LAMP-1 120 minutes post-infection. In A549 cells, 55% and 58% of internalized conidia were found to co-localize with LAMP-1 and CD63 by 24 hours. Cathepsin D also co-localized with internalized conidia in A549 cells. Phagosomes containing conidia were shown to be acidified in both cell types. Less than 1% of the initial inoculum survived in J774 cells by 12 hours post-infection. After 24 hours, 3% of internalized conidia survived in A549 cells and 34% of these had germinated. By 36 hours, the germlings were able to escape the phagosome and form extracellular hyphae without lysis of the host cell.

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Binding and Germination of Aspergillus fumigatus Conidia on Cultured A549 Pneumocytes

Cited by 77 publications

References 18 publications

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

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

Dendritic Cells Transport Conidia and Hyphae ofAspergillus fumigatusfrom the Airways to the Draining Lymph Nodes and Initiate Disparate Th Responses to the Fungus

Aspergillus fumigatus conidia survive and germinate in acidic organelles of A549 epithelial cells

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