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 Aug 18;18(8):1796. doi: 10.3390/ijms18081796.

Abstract

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.

Keywords: ">d-glucan; interleukin-17A; mid-regional proadrenomedullin; mycoses; next-generation sequencing; sepsis; septic shock; β-.

MeSH terms

  • Adrenomedullin / blood
  • Adrenomedullin / immunology
  • Aged
  • Biomarkers / blood
  • Candida / immunology
  • Candida / physiology
  • Female
  • High-Throughput Nucleotide Sequencing / methods*
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immune System / immunology*
  • Interleukin-17 / blood
  • Interleukin-17 / immunology
  • Male
  • Middle Aged
  • Mycoses / diagnosis
  • Mycoses / immunology*
  • Mycoses / microbiology
  • Protein Precursors / blood
  • Protein Precursors / immunology
  • Shock, Septic / blood
  • Shock, Septic / immunology*
  • Shock, Septic / microbiology
  • Time Factors

Substances

  • Biomarkers
  • Interleukin-17
  • Protein Precursors
  • proadrenomedullin
  • Adrenomedullin