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Recognition of Hyphae by Human Plasmacytoid Dendritic Cells Is Mediated by Dectin-2 and Results in Formation of Extracellular Traps


While plasmacytoid dendritic cells (pDCs) are known to be important immune cells involved in protection from viruses and tumors, their role in protection against fungal infections is less clear. Our laboratory has been studying the interplay between pDCs and the fungal pathogen, Aspergillus fumigatus. Our previous work demonstrated that human pDCs bind to and inhibit the growth of A. fumigatus hyphae. Moreover, depletion of pDCs rendered mice very susceptible to experimental infection with A. fumigatus. Here, we show that Dectin-2, a receptor on pDCs, recognizes A. fumigatus hyphae and contributes to cytokine release and antifungal activity. In addition, using confocal and electron microscopy, we demonstrate that upon contact with hyphae, some human pDCs die and form antimicrobial structures called extracellular traps. Finally, using microarrays, we analyzed human pDC gene expression upon A. fumigatus infection and found distinct patterns including the activation of genes previously associated with viral infections and apoptosis. These results provide new insights into the mechanisms by which pDCs might help the immune system when confronted with a fungal invader.


Vyšlo v časopise: Recognition of Hyphae by Human Plasmacytoid Dendritic Cells Is Mediated by Dectin-2 and Results in Formation of Extracellular Traps. PLoS Pathog 11(2): e32767. doi:10.1371/journal.ppat.1004643
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004643

Souhrn

While plasmacytoid dendritic cells (pDCs) are known to be important immune cells involved in protection from viruses and tumors, their role in protection against fungal infections is less clear. Our laboratory has been studying the interplay between pDCs and the fungal pathogen, Aspergillus fumigatus. Our previous work demonstrated that human pDCs bind to and inhibit the growth of A. fumigatus hyphae. Moreover, depletion of pDCs rendered mice very susceptible to experimental infection with A. fumigatus. Here, we show that Dectin-2, a receptor on pDCs, recognizes A. fumigatus hyphae and contributes to cytokine release and antifungal activity. In addition, using confocal and electron microscopy, we demonstrate that upon contact with hyphae, some human pDCs die and form antimicrobial structures called extracellular traps. Finally, using microarrays, we analyzed human pDC gene expression upon A. fumigatus infection and found distinct patterns including the activation of genes previously associated with viral infections and apoptosis. These results provide new insights into the mechanisms by which pDCs might help the immune system when confronted with a fungal invader.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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