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Research Paper

Mucorales spores induce a proinflammatory cytokine response in human mononuclear phagocytes and harbor no rodlet hydrophobins

, , , , , , , , , & show all
Pages 1708-1718 | Received 10 Jan 2017, Accepted 11 Jun 2017, Published online: 08 Aug 2017
 

ABSTRACT

Mucormycoses are life-threatening infections in immunocompromised patients. This study characterizes the response of human mononuclear cells to different Mucorales and Ascomycota. PBMC, monocytes, and monocyte derived dendritic cells (moDCs) from healthy donors were stimulated with resting and germinated stages of Mucorales and Ascomycota. Cytokine response and expression of activation markers were studied. Both inactivated germ tubes and resting spores of Rhizopus arrhizus and other human pathogenic Mucorales species significantly stimulated mRNA synthesis and secretion of proinflammatory cytokines. Moreover, R. arrhizus spores induced the upregulation of co-stimulatory molecules on moDCs and a specific T-helper cell response. Removal of rodlet hydrophobins by hydrofluoric acid treatment of A. fumigatus conidia resulted in enhanced immunogenicity, whereas the cytokine response of PBMCs to dormant R. arrhizus spores was not influenced by hydrofluoric acid. Scanning electron micrographs of Mucorales spores did not exhibit any morphological correlates of rodlet hydrophobins. Taken together, this study revealed striking differences in the response of human mononuclear cells to resting stages of Ascomycota and Mucorales, which may be explained by absence of an immunoprotective hydrophobin layer in Mucorales spores.

This article is referred to by:
Immune responses to Mucorales growth forms: Do we know everything?

Acknowledgments

We thank the Institute for Hygiene and Microbiology (IHM), University of Würzburg for provision of fungal strains and for the opportunity to use their BSL II facilities for culturing and handling of Mucorales isolates.

Funding

This work was supported by the Interdisciplinary Center for Clinical Research (IZKF) Wuerzburg (grant number Z-3/56 to SW) and the DFG Transregio / SFB 124 (project A2, to HE and JL).

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