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Toll-like receptor (TLR) 2 and TLR4 are essential for Aspergillus-induced activation of murine macrophages
Open accessAbstract
Aspergillus fumigatius is a ubiquitous saprophytic fungus that has become the most prevalent airborne fungal pathogen for immunocompromised patients during the last two decades. In this report we have analysed how macrophages recognize this microorganism. Using transfected human HEK 293 cells we demonstrate that NF-kappaB-dependent promoter activation triggered by A. fumigatus is mediated by Toll-like receptors TLR2 and TLR4, whereas no activation was observed in cells overexpressing other distinct TLR proteins (TLR1, TLR3, TLR5-10). Using macrophages derived from mice lacking TLR2 expression, expressing defective TLR4 or both we found that A. fumigatus conidia and hyphae induce NF-kappaB translocation, release of pro-inflammatory molecules, like TNFalpha, and the chemoattractant MIP-2 in a TLR2- and TLR4-dependent manner. Recognition of A. niger and A. fumigatus, was similar in terms of the parameters analysed, suggesting that pathogenic and non-pathogenic aspergilli are sensed by macrophages in a similar fashion. Finally, we found that recruitment of neutrophils is severely impaired in mice lacking both functional TLR2 and TLR4, but is less impaired in single TLR2- or TLR4-deficient mice, providing evidence that both receptors are required for an optimal immune response to Aspergillus in vivo.
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Cited by
Negative regulation of Toll-like receptor-mediated immune responses
Liew, F. Y., Xu, D., Brint, E. K., & O'Neill, L. A. J. (2005) · Nature Reviews Immunology · doi:10.1038/nri1630 · Cited by 1,509
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van de Veerdonk, F. L., Gresnigt, M. S., Romani, L., Netea, M. G., & Latgé, J.-P. (2017) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.90 · Cited by 490
Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation
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Aspergillus fumigatus Triggers Inflammatory Responses by Stage-Specific β-Glucan Display
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“also observed that BMMØs do not produce TNF-a in response to heat-killed resting conidia [20], while two other studies demonstrated that peritoneal macrophages secrete TNF-a in response to heat- or ethanol-killed conidia in a largely TLR-4dependent fashion [18,19].”
ResultThe immune response to fungal infections
Shoham, S., & Levitz, S. M. (2005) · British Journal of Haematology · doi:10.1111/j.1365-2141.2005.05397.x · Cited by 392
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Heinekamp, T., Schmidt, H., Lapp, K., Pähtz, V., Shopova, I., Köster-Eiserfunke, N., Krüger, T., Kniemeyer, O., & Brakhage, A. A. (2015) · Seminars in Immunopathology · doi:10.1007/s00281-014-0465-1 · Cited by 123
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Methods of Controlling Invasive Fungal Infections Using CD8+ T Cells
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Intracellular PRRs Activation in Targeting the Immune Response Against Fungal Infections
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Metadata
- Authors
- Meier, A., Kirschning, C. J., Nikolaus, T., Wagner, H., Heesemann, J., & Ebel, F.
- Venue
- Cellular Microbiology
- Publisher
- Wiley
- Published
- 2003-08
- Volume
- 5
- Issue
- 8
- Pages
- 561-570
- ISSN
- 1462-5814 (ISSN-L)
- 1462-5822
- OpenAlex
- W2005998335
- Cited by
- 296
- References
- 0
- FWCI
- 6.14
- Type
- journal article
- Language
- en
- Open access
- bronze
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