Immune-Response Patterns and Next Generation Sequencing Diagnostics for the Detection of Mycoses in Patients with Septic Shock—Results of a Combined Clinical and Experimental Investigation
by
Sebastian O. Decker 1, Annette Sigl 1, Christian Grumaz 2, Philip Stevens 2,3, Yevhen Vainshtein 2
, Stefan Zimmermann 4, Markus A. Weigand 1, Stefan Hofer 5, Kai Sohn 2,† and Thorsten Brenner 1,*,†
Sebastian O. Decker 1, Annette Sigl 1, Christian Grumaz 2, Philip Stevens 2,3, Yevhen Vainshtein 2, Stefan Zimmermann 4, Markus A. Weigand 1, Stefan Hofer 5, Kai Sohn 2,† and Thorsten Brenner 1,*,†
1
Department of Anesthesiology, Heidelberg University Hospital, 110, Im Neuenheimer Feld, D-69120 Heidelberg, Germany
2
Fraunhofer IGB, 12, Nobelstraße, D-70569 Stuttgart, Germany
3
Noscendo GmbH, 9, Meitnerstraße, D-70563 Stuttgart, Germany
4
Department of Infectious Diseases, Medical Microbiology and Hygiene, Heidelberg University Hospital, 324, Im Neuenheimer Feld, D-69120 Heidelberg, Germany
5
Department of Anesthesiology, Westpfalzklinikum, 1, Hellmut-Hartert-Straß, D-67655 Kaiserslautern, Germany
*
Author to whom correspondence should be addressed.
†
Thorsten Brenner and Kai Sohn share senior authorship.
Int. J. Mol. Sci. 2017, 18(8), 1796; https://doi.org/10.3390/ijms18081796
Received: 14 July 2017 / Revised: 12 August 2017 / Accepted: 14 August 2017 / Published: 18 August 2017
(This article belongs to the Special Issue Sepsis)
Fungi are of increasing importance in sepsis. However, culture-based diagnostic procedures are associated with relevant weaknesses. Therefore, culture- and next-generation sequencing (NGS)-based fungal findings as well as corresponding plasma levels of β-d-glucan, interferon gamma (INF-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-2, -4, -6, -10, -17A, and mid-regional proadrenomedullin (MR-proADM) were evaluated in 50 septic patients at six consecutive time points within 28 days after sepsis onset. Furthermore, immune-response patterns during infections with Candida spp. were studied in a reconstituted human epithelium model. In total, 22% (n = 11) of patients suffered from a fungal infection. An NGS-based diagnostic approach appeared to be suitable for the identification of fungal pathogens in patients suffering from fungemia as well as in patients with negative blood cultures. Moreover, MR-proADM and IL-17A in plasma proved suitable for the identification of patients with a fungal infection. Using RNA-seq., adrenomedullin (ADM) was shown to be a target gene which is upregulated early after an epithelial infection with Candida spp. In summary, an NGS-based diagnostic approach was able to close the diagnostic gap of routinely used culture-based diagnostic procedures, which can be further facilitated by plasmatic measurements of MR-proADM and IL-17A. In addition, ADM was identified as an early target gene in response to epithelial infections with Candida spp.
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Keywords:
mid-regional proadrenomedullin; interleukin-17A; β-d-glucan; next-generation sequencing; mycoses; sepsis; septic shock
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
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MDPI and ACS Style
Decker, S.O.; Sigl, A.; Grumaz, C.; Stevens, P.; Vainshtein, Y.; Zimmermann, S.; Weigand, M.A.; Hofer, S.; Sohn, K.; Brenner, T. Immune-Response Patterns and Next Generation Sequencing Diagnostics for the Detection of Mycoses in Patients with Septic Shock—Results of a Combined Clinical and Experimental Investigation. Int. J. Mol. Sci. 2017, 18, 1796.
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