title: New signaling pathways govern the host response to C. albicans infection in various niches.
abstract: Candida albicans, the major invasive fungal pathogen of humans, can cause both debilitating mucosal infections and fatal invasive infections. Understanding the complex nature of the host-pathogen interaction in each of these contexts is essential to developing desperately needed therapies to treat fungal infections. RNA-seq enables a systems-level understanding of infection by facilitating comprehensive analysis of transcriptomes from multiple species (e.g., host and pathogen) simultaneously. We used RNA-seq to characterize the transcriptomes of both C. albicans and human endothelial cells or oral epithelial cells during in vitro infection. Network analysis of the differentially expressed genes identified the activation of several signaling pathways that have not previously been associated with the host response to fungal pathogens. Using an siRNA knockdown approach, we demonstrate that two of these pathways-platelet-derived growth factor BB (PDGF BB) and neural precursor-cell-expressed developmentally down-regulated protein 9 (NEDD9)-govern the host-pathogen interaction by regulating the uptake of C. albicans by host cells. Using RNA-seq analysis of a mouse model of hematogenously disseminated candidiasis (HDC) and episodes of vulvovaginal candidiasis (VVC) in humans, we found evidence that many of the same signaling pathways are activated during mucosal (VVC) and/or disseminated (HDC) infections in vivo. Our analyses have uncovered several signaling pathways at the interface between C. albicans and host cells in various contexts of infection, and suggest that PDGF BB and NEDD9 play important roles in this interaction. In addition, these data provide a valuable community resource for better understanding host-fungal pathogen interactions.
authors: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90509, USA;
authors: Yaoping
authors: Y
authors: Liu
authors: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA;
authors: Amol C
authors: AC
authors: Shetty
authors: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA;
authors: Jennifer A
authors: JA
authors: Schwartz
authors: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA;
authors: L Latey
authors: LL
authors: Bradford
authors: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA;
authors: Wenjie
authors: W
authors: Xu
authors: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90509, USA; David Geffen School of Medicine at UCLA, Torrance, California 90509, USA.
authors: Qyunh T
authors: QT
authors: Phan
authors: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA;
authors: Priti
authors: P
authors: Kumari
authors: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA;
authors: Anup
authors: A
authors: Mahurkar
authors: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA;
authors: Aaron P
authors: AP
authors: Mitchell
authors: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA;
authors: Jacques
authors: J
authors: Ravel
authors: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA;
authors: Claire M
authors: CM
authors: Fraser
authors: Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California 90509, USA; David Geffen School of Medicine at UCLA, Torrance, California 90509, USA.
authors: Scott G
authors: SG
authors: Filler
authors: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA;
authors: Vincent M
authors: VM
authors: Bruno
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000077214:Becaplermin; D002176:Candida albicans / Q000472:pathogenicity; D002177:Candidiasis / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C099942:NEDD9 protein, human; D010750:Phosphoproteins; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin