Identification by DNA microarray of genes involved in <i>Candida albicans</i>‐treated gingival epithelial cells

Ikuta, Tonami; Bhawal, Ujjal K.; Tsushima, Katsumasa; Aoki, Akinobu; Kuboyama, Noboru; Abiko, Yoshimitsu

doi:10.1111/j.1600-0714.2012.01149.x

Cited by 8 publications

(5 citation statements)

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“…Early microarray studies analyzed C. albicans gene expression during invasion of epithelial cells ( Moyes et al, 2010 ; Ikuta et al, 2012 ), as well as epithelial cell responses to infection by C. albicans ( Sandovsky-Losica et al, 2006 ; Zakikhany et al, 2007 ; Park et al, 2009 ). More recently, the more sensitive technique of RNA-seq has been employed to characterize the transcriptomes of both C. albicans and host cells during VVC infection in human subjects.…”

Section: Host-fungal Interaction Induces Non-protective Immune Responsementioning

confidence: 99%

It Takes Two to Tango: How a Dysregulation of the Innate Immunity, Coupled With Candida Virulence, Triggers VVC Onset

2021

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Vulvovaginal candidiasis (VVC) is a symptomatic inflammation of the vagina mainly caused by C. albicans. Other species, such as C. parapsilosis, C. glabrata, C. tropicalis, and C. krusei, are mainly associated to the recurrent form of the disease (RVVC), although with a lower frequency. In its yeast form, C. albicans is tolerated by the vaginal epithelium, but switching to the invasive hyphal form, co-regulated with the expression of genes encoding virulence factors such as secreted aspartyl proteases (Sap) and candidalysin, allows for tissue damage. Vaginal epithelial cells play an important role by impairing C. albicans tissue invasion through several mechanisms such as epithelial shedding, secretion of mucin and strong interepithelial cell connections. However, morphotype switching coupled to increasing of the fungal burden can overcome the tolerance threshold and trigger an intense inflammatory response. Pathological inflammation is believed to be facilitated by an altered vaginal microbiome, i.e., Lactobacillus dysbiosis. Notwithstanding the damage caused by the fungus itself, the host response to the fungus plays an important role in the onset of VVC, exacerbating fungal-mediated damage. This response can be triggered by host PRR-fungal PAMP interaction and other more complex mechanisms (i.e., Sap-mediated NLRP3 activation and candidalysin), ultimately leading to strong neutrophil recruitment. However, recruited neutrophils appear to be ineffective at reducing fungal burden and invasion; therefore, they seem to contribute more to the symptoms associated with vaginitis than to protection against the disease. Recently, two aspects of the vulvovaginal environment have been found to associate with VVC and induce neutrophil anergy in vitro: perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) and heparan sulfate. Interestingly, CAGTA antibodies have also been found with higher frequency in VVC as compared to asymptomatic colonized women. This review highlights and discusses recent advances on understanding the VVC pathogenesis mechanisms as well as the role of host defenses during the disease.

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Section: Host-fungal Interaction Induces Non-protective Immune Responsementioning

confidence: 99%

It Takes Two to Tango: How a Dysregulation of the Innate Immunity, Coupled With Candida Virulence, Triggers VVC Onset

2021

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“…Understanding how ECs interact with C. albicans is of paramount importance in determining how ECs respond to fungal-induced damage. Earlier work characterized the global transcriptional changes in C. albicans cells during infection of oral ECs [15]; however, the transcriptional profile of ECs during C. albicans infection has only recently been addressed [16]. …”

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confidence: 99%

Protection Against Epithelial Damage During Candida albicans Infection Is Mediated by PI3K/Akt and Mammalian Target of Rapamycin Signaling

Moyes

Shen

Murciano

et al. 2013

The Journal of Infectious Diseases

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Background. The ability of epithelial cells (ECs) to discriminate between commensal and pathogenic microbes is essential for healthy living. Key to these interactions are mucosal epithelial responses to pathogen-induced damage.Methods. Using reconstituted oral epithelium, we assessed epithelial gene transcriptional responses to Candida albicans infection by microarray. Signal pathway activation was monitored by Western blotting and transcription factor enzyme-linked immunosorbent assay, and the role of these pathways in C. albicans–induced damage protection was determined using chemical inhibitors.Results. Transcript profiling demonstrated early upregulation of epithelial genes involved in immune responses. Many of these genes constituted components of signaling pathways, but only NF-κB, MAPK, and PI3K/Akt pathways were functionally activated. We demonstrate that PI3K/Akt signaling is independent of NF-κB and MAPK signaling and plays a key role in epithelial immune activation and damage protection via mammalian target of rapamycin (mTOR) activation.Conclusions. PI3K/Akt/mTOR signaling may play a critical role in protecting epithelial cells from damage during mucosal fungal infections independent of NF-κB or MAPK signaling.

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“…Previous studies have used microarrays to individually examine the transcriptional response of C. albicans to endothelial or epithelial cells (Müller et al 2007;Barker et al 2008;Lim et al 2011;Ikuta et al 2012;Moyes et al 2014), as well as the transcriptional response of these host cells to infection by C. albicans (Sandovsky-Losica et al 2006;Zakikhany et al 2007;Park et al 2009;Martin et al 2011;Wachtler et al 2011). Although these studies have contributed to our understanding of the interaction between pathogen and host, the full catalog of transcriptional changes is not complete owing to the limitations of microarrays, which include limited dynamic range and poor sensitivity to analyze low abundance transcripts.…”

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confidence: 99%

New signaling pathways govern the host response to C. albicans infection in various niches

et al. 2015

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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.

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Identification by DNA microarray of genes involved in Candida albicans‐treated gingival epithelial cells

Abstract: These findings indicate that the molecular mechanisms underlying the IL-8 response of HGECs to C. albicans infection likely involve multiple converging signal transduction pathways.

Cited by 8 publications

References 43 publications

It Takes Two to Tango: How a Dysregulation of the Innate Immunity, Coupled With Candida Virulence, Triggers VVC Onset

It Takes Two to Tango: How a Dysregulation of the Innate Immunity, Coupled With Candida Virulence, Triggers VVC Onset

Protection Against Epithelial Damage During Candida albicans Infection Is Mediated by PI3K/Akt and Mammalian Target of Rapamycin Signaling

New signaling pathways govern the host response to C. albicans infection in various niches

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