RNA-Seq Profile Reveals Th-1 and Th-17-Type of Immune Responses in Mice Infected Systemically with Aspergillus fumigatus.

Mycopathologia
Authors
Keywords
Abstract

With the increasing numbers of immunocompromised hosts, Aspergillus fumigatus emerges as a lethal opportunistic fungal pathogen. Understanding innate and acquired immunity responses of the host is important for a better therapeutic strategy to deal with aspergillosis patients. To determine the transcriptome in the kidneys in aspergillosis, we employed RNA-Seq to obtain single 76-base reads of whole-genome transcripts of murine kidneys on a temporal basis (days 0; uninfected, 1, 2, 3 and 8) during invasive aspergillosis. A total of 6284 transcripts were downregulated, and 5602 were upregulated compared to baseline expression. Gene ontology enrichment analysis identified genes involved in innate and adaptive immune response, as well as iron binding and homeostasis, among others. Our results showed activation of pathogen recognition receptors, e.g., β-defensins, C-type lectins (e.g., dectin-1), Toll-like receptors (TLR-2, TLR-3, TLR-8, TLR-9 and TLR-13), as well as Ptx-3 and C-reactive protein among the soluble receptors. Upregulated transcripts encoding various differentiating cytokines and effector proinflammatory cytokines, as well as those encoding for chemokines and chemokine receptors, revealed Th-1 and Th-17-type immune responses. These studies form a basic dataset for experimental prioritization, including other target organs, to determine the global response of the host against Aspergillus infection.

Year of Publication
2018
Journal
Mycopathologia
Volume
183
Issue
4
Pages
645-658
Date Published
2018 Aug
ISSN
1573-0832
DOI
10.1007/s11046-018-0254-9
PubMed ID
29500637
PubMed Central ID
PMC6067991
Links
Grant list
R21 AI085566 / AI / NIAID NIH HHS / United States
1R21AI85566-01 / National Institute of Allergy and Infectious Diseases