Dual transcriptome of the immediate neutrophil and Candida albicans interplay

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Background: Neutrophils are traditionally considered transcriptionally inactive. Compared to other immune cells, little is known about their transcriptional profile during interaction with pathogens. Methods: We analyzed the meta-transcriptome of the neutrophil-Candida albicans interplay and the transcriptome of C. albicans challenged with neutrophil extracellular traps (NETs) by RNA-Seq, considering yeast and hypha individually in each approach. Results: The neutrophil response to C. albicans yeast and hyphae was dominated by a morphotype-independent core response. However, 11% of all differentially expressed genes were regulated in a specific manner when neutrophils encountered the hyphal form of C. albicans. While involving genes for transcriptional regulators, receptors, and cytokines, the neutrophil core response lacked typical antimicrobial effectors genes. Genes of the NOD-like receptor pathway, including NLRP3, were enriched. Neutrophil- and NET-provoked responses in C. albicans differed. At the same time, the Candida transcriptome upon neutrophil encounter and upon NET challenge included genes from various metabolic processes and indicate a mutual role of the regulators Tup1p, Efg1p, Hap43p, and Cap1p. Upon challenge with neutrophils and NETs, the overall Candida response was partially morphotype-specific. Yet again, actual oppositional regulation in yeasts and hyphae was only detected for the arginine metabolism in neutrophil-infecting C. albicans. Conclusions: Taken together, our study provides a comprehensive and quantitative transcript profile of the neutrophil-C. albicans interaction. By considering the two major appearances of both, neutrophils and C. albicans, our study reveals yet undescribed insights into this medically relevant encounter. Hence, our findings will facilitate future research and potentially inspire novel therapy developments.

Detaljer

Författare
  • Maria J. Niemiec
  • Christian Grumaz
  • David Ermert
  • Christiane Desel
  • Madhu Shankar
  • José Pedro Lopes
  • Ian G. Mills
  • Philip Stevens
  • Kai Sohn
  • Constantin F. Urban
Enheter & grupper
Externa organisationer
  • Umeå University
  • Leibniz Institute for Natural Product Research and Infection Biology
  • Fraunhofer Institute for Interfacial Engineering and Biotechnology
  • University Hospital Erlangen
  • University of Oxford
  • Queen's University Belfast
  • University of Stuttgart
  • University of Vienna
  • Friedrich-Alexander University Erlangen-Nürnberg
  • University of Oslo
  • Norwegian Radium Hospital
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Mikrobiologi inom det medicinska området
  • Cell- och molekylärbiologi

Nyckelord

Originalspråkengelska
Artikelnummer696
TidskriftBMC Genomics
Volym18
Utgivningsnummer1
StatusPublished - 2017 sep 6
PublikationskategoriForskning
Peer review utfördJa