Characterisation of the phagocytic uptake of Aspergillus fumigatus conidia by macrophages

Luther, Kathrin; Rohde, Manfred; Sturm, Katrin; Kotz, Andrea; Heesemann, Jürgen; Ebel, Frank

doi:10.1016/j.micinf.2007.11.001

Cited by 29 publications

(29 citation statements)

References 29 publications

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“…Moreover, in accordance with data in animals showing the importance of mouse NK cells for the clearance of A. fumigatus from the lungs (8), we demonstrated that human NK cells exert direct cytotoxicity against germlings; however, this is not the case with conidia. Both cytokine induction and antifungal activity suggest that NK cells perceive only germinated morphologies of A. fumigatus, recognizing that the fungus has escaped the first line of host defense, provided by alveolar macrophages and neutrophils (31)(32)(33). Priming of NK cells with rhIL-2 seems to be a prerequisite for NK cell-fungus interaction, suggesting an important role for cytokine-producing immune cells in the interplay of NK cells with A. fumigatus.…”

Section: Discussionmentioning

confidence: 99%

Human NK Cells Display Important Antifungal Activity againstAspergillus fumigatus, Which Is Directly Mediated by IFN-γ Release

Bouzani

et al. 2011

The Journal of Immunology

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108

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Despite the strong interest in the NK cell-mediated immunity toward malignant cells and viruses, there is a relative lack of data on the interplay between NK cells and filamentous fungi, especially Aspergillus fumigatus, which is the major cause of invasive aspergillosis. By studying the in vitro interaction between human NK cells and A. fumigatus, we found only germinated morphologies to be highly immunogenic, able to induce a Th1-like response, and capable of upregulating cytokines such as IFN-γ and TNF-α. Moreover, priming NK cells with human rIL-2 and stimulating NK cells by direct NK cell–pathogen contact were essential to induce damage against A. fumigatus. However, the most interesting finding was that NK cells did not mediate anti-Aspergillus cytotoxicity through degranulation of their cytotoxic proteins (perforin, granzymes, granulysine), but via an alternative mechanism involving soluble factor(s). To our knowledge, our study is the first to demonstrate that IFN-γ, released by NK cells, directly damages A. fumigatus, attributing new properties to both human NK cells and IFN-γ and suggesting them as possible therapeutic tools against IA.

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Section: Discussionmentioning

confidence: 99%

Human NK Cells Display Important Antifungal Activity againstAspergillus fumigatus, Which Is Directly Mediated by IFN-γ Release

Bouzani

et al. 2011

The Journal of Immunology

Self Cite

112

108

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“…It also told the same tendency from the quantifying score of histopathological damage (B, n=3). [5,28,32] . While PMNs are essential for pathogen eradication, excessive release of oxidants and proteases may be responsible for organ injury as well as fungal sepsis [33][34][35][36] .…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, significant changes in the cytokine levels of the lung homogenates were recorded among all three groups, with markedly elevated levels of both TNF-α and IL-10 at 24, 48, and 72 h with AMB plus NAC treatment. Studies of the IPA murine model have demonstrated that resistance to infection is associated with the production of Th1 cytokines, whereas Th2-cytokine release was correlated with disease progression [32,38,39] . Aihara et al previously reported that NAC could increase Th1/Th2 cytokine levels in vitro [40] .…”

Section: Discussionmentioning

confidence: 99%

NAC is associated with additional alleviation of lung injury induced by invasive pulmonary aspergillosis in a neutropenic model

Jian

et al. 2009

Acta Pharmacol Sin

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Aim: Neutropenic individuals are at high risk for invasive pulmonary aspergillosis (IPA), a life-threatening infection. To evaluate the therapeutic potential of antioxidants, IPA was induced in neutropenic mice and the effect of N-acetyl-l-cysteine (NAC) on oxidative stress levels and lung injury was analyzed. Methods: Mice were pretreated with three daily intraperitoneal injections of 150 mg/kg cyclophosphamide, followed by intratracheal inoculation with 4.5×10 6 conidia of Aspergillus fumigatus. The infected mice were then randomly assigned to an amphotericin B (AMB) group, an AMB plus NAC group, or an untreated control (C) group. In each group, the duration of treatment was 24, 48, or 72 h, and activities such as appearance, feeding, and dermal temperature were observed throughout the experiment. Sera and lung tissues were collected and analyzed by quantitative enzyme-linked immunosorbent assay (ELISA) for total protein, superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) levels. The wet/dry weight ratio of the lung was also calculated and lung sections were stained with hematoxylin-eosin for pathological examination and with methenamine silver stain for fungus detection. Results: Compared with the mice untreated with NAC, mice in the AMB plus NAC group had increased SOD and reduced MDA levels both systemically and locally at 24, 48, and 72 h after inoculation with conidia. NAC treatment also decreased the pulmonary protein content at 48 and 72 h and the lung wet/dry weight ratio at 24 and 48 h. Additionally, NAC enhanced pulmonary production of TNF-α and IL-10 at 24 h and 48 h. Conclusion: In combination with antifungal therapy, NAC treatment can alleviate oxidative stress and lung injury associated with IPA in neutropenic mice.

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“…In one study, two broad-range TKIs (genistein and AG18) and inhibitors that specifically blocked src kinases strongly reduced A. fumigatus conidia uptake by human and murine macrophages. 152 This could have implications for Aspergillus virulence as phagocytosis of conidia (e.g., in the lung) is required for their elimination.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

“…One possible explanation is that for A. fumigatus, the fungus is able to survive on dead/decaying matter and is relatively resistant to nutrient stress. 152 …”

Section: Autophagy Inhibitorsmentioning

confidence: 99%

Direct effects of non-antifungal agents used in cancer chemotherapy and organ transplantation on the development and virulence ofCandidaandAspergillusspecies

2011

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Characterisation of the phagocytic uptake of Aspergillus fumigatus conidia by macrophages

Cited by 29 publications

References 29 publications

Human NK Cells Display Important Antifungal Activity againstAspergillus fumigatus, Which Is Directly Mediated by IFN-γ Release

Human NK Cells Display Important Antifungal Activity againstAspergillus fumigatus, Which Is Directly Mediated by IFN-γ Release

NAC is associated with additional alleviation of lung injury induced by invasive pulmonary aspergillosis in a neutropenic model

Direct effects of non-antifungal agents used in cancer chemotherapy and organ transplantation on the development and virulence ofCandidaandAspergillusspecies

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